A Review of Protective Effects of Exercise on Cognitive Impairments Induced by Sleep Deprivation in Female Rats


Hakimeh Saadati 1 , *

1 Department of Physiology, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, IR Iran

How to Cite: Saadati H. A Review of Protective Effects of Exercise on Cognitive Impairments Induced by Sleep Deprivation in Female Rats, Arch Neurosci. 2017 ; 4(3):e13250. doi: 10.5812/archneurosci.13250.


Archives of Neuroscience: 4 (3); e13250
Published Online: May 21, 2017
Article Type: Review Article
Received: October 19, 2016
Accepted: April 29, 2017


Sleep is an important factor in memory consolidation and brain health. In addition, sleep disorder is a common complaint among females in comparison with males. In menopausal females, to relieve sleep disturbances and other menopausal symptoms, hormone therapy may be used. Furthermore, although estrogen had helpful effects on the brain performance, hormone replacement therapy augmented unfavorable cardiovascular and oncological side effects. It is implied that exercise is a powerful non-pharmacological intervention that can develop the cognitive performances. The current study used the behavioral, physiological, and molecular evidence supporting these views.

1. Introduction and Statement of the Problem

Similar to other physiological functions, sleep regulation is carried out by the circadian clock in the hypothalamus. Sleep is characterized by 2 main phases: Non-rapid-eye movement (NREM) and sleep pursued by rapid-eye movement (REM) sleep. Sleep plays a vital role in health and performance. Many people diminish the amount of sleep time for business or lifestyle reasons in the modernized society. Evidence from experimental researches in humans indicate that sleep loss (less than 7 to 8 hours of sleep each night) causes significant impairment in cardiovascular, immune, endocrine and cognitive performances (1, 2). The national sleep foundation (NFS) reported that 7 to 8 hours of sleep is necessary for the best cognitive performance in adults (3). Other experiments confirmed the beneficial effects of sleep on declarative and non-declarative memory. It seems that sleep is the main factor in the acquisition and consolidation of memory (4, 5). Therefore, sleep deprivation (SD) impairs spatial (6, 7), emotional (8), and working memories (9), and augments anxiety like behaviors (10). As a result, hippocampus is very sensitive to sleep loss (11, 12). Accordingly, sleep deprivation negatively impacts long-term potentiation (12, 13), which is established as a form of synaptic plasticity (14, 15). Other studies demonstrated that generation and preservation of long-term potentiating (LTP) and spatial learning and memory are impaired by sleep deprivation. Sleep deprivation also decreases trophic factors such as brain derived neurotrophic factors (BDNF) level in the hippocampus of male (16) and female (6, 13, 17-19) rats.

It seems that cognitive functions (20), quality, and pattern of sleep (21) are different in the 2 genders. On the whole, hormonal factors -particularly estrogen levels- can change sleep patterns (22). It is also noticeable that changes in cognitive performance and sleep pattern and quality are often associated with sex hormones (23, 24). These findings highlight the importance of sex hormones in sleep regulation in the menopause period in females who indicate low levels of circulating estrogen (25) and are more sensitive to deleterious effects of sleep deficit on cognitive function (26).

Sleep disturbances are more common among females in comparison with males. Additionally, disturbed sleep is a more frequent compliant of menopausal and post-menopausal females (2, 25).

Additionally, regardless of the helpful effects of sexual hormones on the brain health, hormone replacement therapy has cardiovascular and oncological side effects (27); there is conspicuous concentration to develop helpful therapeutic methods to improve deteriorations associated with sleep deprivation.

The positive effects of physical activity on various physiological systems such as the nervous system and brain health are well displayed (28). Exercise can enhance cognitive performance and cell proliferation in the hippocampus (29).

Physical activity can develop some forms of synaptic plasticity such as LTP (28) and this protocol can also increase the level of BDNF (30).

Additionally, exercise can preserve memory impairments (6) and improve LTP (13) in neurodegenerative diseases and estrogen deprivation periods (31).Other investigations revealed that regular activity can prevent the SD-induced impairments of cognitive function, synaptic plasticity, and signaling molecules in the hippocampus of male (16) and female rats (6, 13, 18, 19).

Given the conflicting effects of SD and regular physical activity on cognitive performances, it is rational to recommend that preconditioning the brain with regular exercise could compensate or weaken the harmful effects of SD on learning and memory. Specifically, this review was designed to assess the effects of physical exercise on cognitive impairments associated with SD in female rats.

2. Sleep, Memory, and Synaptic Plasticity

Several studies established that sleep had valuable effects on declarative and procedural memory in various tasks. During sleep, earlier encoded memory traces are reactivated and finally consolidated in the neocortex as a result of certain neuromodulators (eg, neurotransmitters) and cellular processes (eg, gene expression and protein translation). Several literature support a long-term integrative or consolidated function for different stages of sleep in newly obtained information (32, 33).

3. Modified Multiple Platform Paradigm

Sleep deprivation is accomplished by different techniques. One of these methods is modified multiple platform also recognized as the water tank or columns-in-water or inverted flowerpot model. Even though this method is well-organized in suppressing about 95% of REM sleep, it can also intervene with NREM sleep (34). As a result, the mentioned technique was based on a feature of REM sleep as muscle atonia (35). However, the fact that animals are restricted to the single platform introduces isolation stress as a confounding factor. Thereafter, the multiple platforms method was developed to alleviate movement restriction and social isolation associated with the single flowerpot method, thereby allowing the animals to move among several platforms. Later, the multiple platform technique was extended into the less disturbing modified multiple platform process, which allows animals from the same cage to experience SD together (Figure 1). The novel modified multiple platform diminishes psychosocial, immobilization, and separation stress as confounders often observed in the previous flowerpot models (34-36).

4. Sleep Deprivation and Cognitive Disorders

The chronic lack of sleep and sleep disorders became one of the typical features of the society. An ample body of evidence confirms a prominent relationship between SD and memory destruction both in animals and humans in different paradigms (7, 37, 38). Several experiments established the significant correlation between REM sleep and cognitive performances in male and female animals. Animals that experienced SD indicated significant cognitive impairments in various paradigms such as radial ram water maze (16), Morris water maze (MWM) (6, 17, 19), and the plus-maze discriminative avoidance task (39). The negative effects of SD on emotional memory of mice were previously recognized (8). The ability of mice to retain novel information and consolidate memory was interrupted by SD (40). Based on the results of previous studies, it seems that ovariectomized (OVX) female rats are more susceptible than intact animals to the harmful effects of SD on cognitive functions (6, 13, 18, 19). Additionally, these finding are compatible with those of human studies indicating that menopausal females were susceptible to negative effects of sleep loss (41). However, females in menopause period are more susceptible to the deleterious effects of poor sleep on cognitive performances (25, 42).

The results of the studies imply that sex hormones have strong neuroprotective functions against different neuronal and brain injuries (41, 43, 44), though the mechanism of occurrence is not completely understood.

Moreover, LTP is impaired after various periods of SD (13). The negative effect of SD on synaptic plasticity is thought to be a result of the fundamental harmful alterations in intracellular signaling molecules and receptors such as NMDA (N-Methyl-D-aspartic acid or N-Methyl-D-aspartate) and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (9, 45). For example, NMDA receptors that are important for the generation of LTP indicated harmful changes in receptor subunit formation and modulation after 24 hours of REM-SD (45). Another study indicated that phosphorylation and membrane trafficking of hippocampal glutamate AMPA receptors, which are critical in initiating synaptic plasticity, impaired after 12 hours of SD (9). Molecular studies also show that 8, 24, and 48 hours of SD can impair the expression of key signaling molecules and growth factors (eg, MAPK, CREB, and BDNF) related in LTP and cognitive function in the hippocampus (16, 46-48). Indeed, the reduced cognitive functions generated by sleep loss and/or business factors are approved as a dominant popular health and safety topics with abundant economic and social charges (1).

The results of the current experiment indicated that induction and maintenance of LTP in the hippocampus of all female rats impaired after 72 hours of SD, but ovariectomized group exhibited more deficiency, compared with the intact female animals; although this difference was insignificant (13).

Some human studies reported the augmented vulnerability of females during menopause to the harmful impacts of sleep deficits on psychological (49) and cognitive functions and brain health (50). The effects of estrogen on hippocampal function were further approved by experiments indicating augmented dendritic spine density, phosphorylation, and levels of NMDA receptor, as well as a raise in the induction of LTP in the hippocampus of female rats during pro-estrus period of estrous phase (51, 52). The estrogen loss was ultimately suggested as the fundamental candidate for mediating the higher vulnerability of OVX animals to the negative impacts of sleep deficits on cognition, brain health, and synaptic plasticity.

Additionally, previous findings also showed that OVX rats were more sensitive than intact animals to the harmful effect of sleep loss on BDNF levels (18). In the central nervous system (CNS), estrogen has widespread and different interactions with growth factors (53). The putative estrogen-sensitive response element (ERE) in the BDNF gene caused many researchers to propose that the regulation of BDNF expression in the CNS may be achieved through estrogen. Therefore, BDNF is considered as a main mediator of estrogen effects on cognitive function and hippocampal physiology with potential neuroprotective properties (54).

5. Exercise Recovers Cognitive Impairments in the Sleep-Deprived Female Rats

Physical exercise is thought to have useful impacts on cognitive performance. Several documents indicate that physical exercise can compensate deteriorations associated with SD in short- and long-term memories in male (16, 55) and female animals (6, 19). These data suggest that the helpful effects of regular activity on cognitive deficits caused by SD may be mediated by BDNF and other signaling molecules in the hippocampus.

Previous results indicated that 72 hours SD can impair the spatial learning of the OVX rats and spatial memory of both OVX and intact female animals (6, 56). Therefore, pre- and post-learning sleep deprivations also disrupt the short-term and long-term memory in female animals (6, 19). Nevertheless, animals that underwent regular treadmill exercise before SD had a recovered function in MWM test than the sleep-deprived rats. The beneficial effect of regular exercise was outstanding in OVX rats and the rats that did exercise before SD indicated an increased acquisition rate than SD group (6, 19).

It is demonstrated that regular exercise has constructive effects on the cognitive failure associated with aging (57). Regular activities can also promote cognitive performance in neurodegenerative diseases such as the Alzheimer disease (58, 59) and brain ischemia (60).

Although it is implied that physical activity recovers cognitive distraction in the sleep-deprived animals, at the same time, the effects of physical activity on cognitive functions is controversial. The results of some studies suggest that exercise can protect the brain during sleep deprivation or other neurodegenerative diseases (16, 55). However, some findings indicated that neither intentional nor involuntary exercises developed cognitive performance, and were not helpful in learning and retention in different hippocampal functions in normal experimental animals (61-65). Previously, it was indicated that voluntary exercise can promote the cell propagation in hippocampus and improve spatial navigation and aversive memory problems in the estrogen-deprived animals (29). These incompatible data may be due to some differences such as length and time of exercise training, and type and intensity of the experiment used. In addition, such different findings may be due to the diversity in age and strain of the examined animals.

6. Exercise Prevents Synaptic Plasticity Impairments Induced by Sleep Deprivation

The positive effects of regular exercise on deleterious behavioral, synaptic, and molecular problems caused by sleep loss were shown in several studies (6, 13, 16, 18). These experimental studies demonstrated that the advantageous influences of regular activity at the cellular level were possibly as a result of its potential to augment the generation of BDNF and other signaling molecules in the sleep-deprived animals.

However, in the previous studies, treadmill exercise could compensate induction and maintenance of LTP deficits induced by sleep deprivation in the hippocampus of female (13) and male (16) rats. In addition, these results in a treadmill running model showed that exercise training alone had no meaningful effects on the LTP induction in normal animals (13). These findings support the claim that forced exercise may limit its capability to improve only in the existence of cognitive deficits. These investigations revealed that the production of BDNF and other signaling molecules, as a basic molecular mechanism of brain plasticity, increased in the sleep-deprived male rats that did exercise (16, 55).

However, it is extensively reported that running exercise alleviates different ischemic brain injury; facilitates recovery from injury, and raises protection against brain insult (60, 66), though the underlying mechanisms are poorly understood. These benefits are best delineated with respect to the promotion of neurotrophic factors expression such as BDNF (30). Although some exercise interventions indicated the significant promotion of cognitive function, learning, and memory function, and brain health (28, 63, 66-68), other studies revealed the lack of improvement of cognitive functions by exercise training (16, 55, 69). This disagreement may be due to the differences in the duration of training, type of activity, and intensity of the accomplished training exercises.

7. Effect of Regular Exercise and/or Sleep Deprivation on BDNF Levels in the Hippocampus of Female Rats

Data from molecular assays showed that hippocampal BDNF protein levels and mRNA expression of OVX female animals was decreased by sleep deprivation, meanwhile sleep-deprived animals that did exercise had higher hippocampal expression of mRNA and protein levels of BDNF (18). In addition, other experiments revealed that exercise training reversed deleterious alternations of signaling molecules such as BDNF in the hippocampus of sleep-deprived male rats (16, 55).

It was previously indicated that estrogen replacement therapy during postmenopausal in females can restrict the lessening of cognitive performance (70) and can diminish the danger of Alzheimer disease (71). Moreover ovarian steroid hormones increase the levels of BDNF protein and mRNA expression (54). Another document revealed that variations in emotion, sleep, as well as general, physical, and mental health during menopause in females were not considerable (72).

It is well documented that the function of BDNF in synaptic plasticity might be the main factor for protecting neural plasticity and disease support at the aging period and in neurodegenerative disorders (73). It is assumed that the correlation among steroid hormones, regular activity, and hippocampal BDNF level is possibly an important factor to defend brain healthiness (74).

Furthermore, physical exercise could avoid the diminishing effect of SD on BDNF level in the OVX female animals, although this running protocol did not influence the mRNA and protein levels of BDNF in the hippocampus of normal animals that did exercise (18). It was in agreement with other findings that demonstrated the lack of modified levels of hippocampal BDNF in groups that did exercise (69). These data support the notion that perhaps involuntary exercise training applies beneficial effects on insults or deteriorations such as sleep deficits, brain ischemia, and neurodegenerative diseases.

Therefore, several findings indicated that both voluntary and involuntary running can amplify the hippocampal trophic factor and other signaling molecules (16, 28).

Results of investigations about the effect of BDNF function on hippocampus performances generated inconsistent results. It is indicated that brain-derived neurotrophic factors play a main role in the functions associated with hippocampus (75, 76). On the contrary, other studies revealed that central application of BDNF did not improve the acquisition rate of spatial learning-damaged rats (77). Therefore, difference in techniques, including the duration and kind of regular activity and experimental procedure might cause diverse results.

8. Conclusions

In conclusion,

1) Evidence indicates that involuntary running can diminish SD-caused deficits of cognitive functions and synaptic plasticity in the male and female animals.

2) Molecular data indicated that physical activity used a defensive effect against the functions associated with hippocampus and synaptic plasticity destructions induced by sleep deprivation maybe by increasing BDNF protein, mRNA expression, and other signaling molecules in the hippocampus of OVX female rats.



  • 1.

    McCoy JG, Strecker RE. The cognitive cost of sleep lost. Neurobiol Learn Mem. 2011; 96(4) : 564 -82 [DOI][PubMed]

  • 2.

    Luyster FS, Strollo PJ, Zee PC, Walsh JK, Boards of Directors of the American Academy of Sleep M, the Sleep Research S. Sleep: a health imperative. Sleep. 2012; 35(6) : 727 -34 [DOI][PubMed]

  • 3.

    Centers for Disease C. Effect of short sleep duration on daily activities--United States, 2005-2008. MMWR Morb Mortal Wkly Rep. 2011; 60(8) : 239 -42 [PubMed]

  • 4.

    Blissitt PA. Sleep, memory, and learning. J Neurosci Nurs. 2001; 33(4) : 208 -15 [PubMed]

  • 5.

    Diekelmann S, Born J. The memory function of sleep. Nat Rev Neurosci. 2010; 11(2)[DOI]

  • 6.

    Saadati H, Esmaeili-Mahani S, Esmaeilpour K, Nazeri M, Mazhari S, Sheibani V. Exercise improves learning and memory impairments in sleep deprived female rats. Physiol Behav. 2015; 138 : 285 -91 [DOI][PubMed]

  • 7.

    Tartar JL, McKenna JT, Ward CP, McCarley RW, Strecker RE, Brown RE. Sleep fragmentation reduces hippocampal CA1 pyramidal cell excitability and response to adenosine. Neurosci Lett. 2010; 469(1) : 1 -5 [DOI][PubMed]

  • 8.

    Fernandes-Santos L, Patti CL, Zanin KA, Fernandes HA, Tufik S, Andersen ML, et al. Sleep deprivation impairs emotional memory retrieval in mice: influence of sex. Prog Neuropsychopharmacol Biol Psychiatry. 2012; 38(2) : 216 -22 [DOI][PubMed]

  • 9.

    Hagewoud R, Havekes R, Novati A, Keijser JN, Van der Zee EA, Meerlo P. Sleep deprivation impairs spatial working memory and reduces hippocampal AMPA receptor phosphorylation. J Sleep Res. 2010; 19(2) : 280 -8 [DOI][PubMed]

  • 10.

    Vollert C, Zagaar M, Hovatta I, Taneja M, Vu A, Dao A, et al. Exercise prevents sleep deprivation-associated anxiety-like behavior in rats: potential role of oxidative stress mechanisms. Behav Brain Res. 2011; 224(2) : 233 -40 [DOI][PubMed]

  • 11.

    Campbell IG, Guinan MJ, Horowitz JM. Sleep deprivation impairs long-term potentiation in rat hippocampal slices. J Neurophysiol. 2002; 88(2) : 1073 -6 [PubMed]

  • 12.

    Kim EY, Mahmoud GS, Grover LM. REM sleep deprivation inhibits LTP in vivo in area CA1 of rat hippocampus. Neurosci Lett. 2005; 388(3) : 163 -7 [DOI][PubMed]

  • 13.

    Saadati H, Sheibani V, Esmaeili-Mahani S, Hajali V, Mazhari S. Prior regular exercise prevents synaptic plasticity impairment in sleep deprived female rats. Brain Res Bull. 2014; 108 : 100 -5 [DOI][PubMed]

  • 14.

    Bliss TV, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993; 361(6407) : 31 -9 [DOI][PubMed]

  • 15.

    Malenka RC, Bear MF. LTP and LTD: an embarrassment of riches. Neuron. 2004; 44(1) : 5 -21 [DOI][PubMed]

  • 16.

    Zagaar M, Alhaider I, Dao A, Levine A, Alkarawi A, Alzubaidy M, et al. The beneficial effects of regular exercise on cognition in REM sleep deprivation: behavioral, electrophysiological and molecular evidence. Neurobiol Dis. 2012; 45(3) : 1153 -62 [DOI][PubMed]

  • 17.

    Hajali V, Sheibani V, Mahani SE, Hajializadeh Z, Shabani M, Aliabadi HP, et al. Ovariectomy does not exacerbate the negative effects of sleep deprivation on synaptic plasticity in rats. Physiol Behav. 2015; 144 : 73 -81 [DOI][PubMed]

  • 18.

    Saadati H, Sheibani V, Esmaeili-Mahani S, Darvishzadeh-Mahani F, Mazhari S. Prior regular exercise reverses the decreased effects of sleep deprivation on brain-derived neurotrophic factor levels in the hippocampus of ovariectomized female rats. Regul Pept. 2014; 194-195 : 11 -5 [DOI][PubMed]

  • 19.

    Salari M, Sheibani V, Saadati H, Pourrahimi A, khaksarihadad M, Esmaeelpour K, et al. The compensatory effect of regular exercise on long-term memory impairment in sleep deprived female rats. Behav Processes. 2015; 119 : 50 -7 [DOI][PubMed]

  • 20.

    Maren S, De Oca B, Fanselow MS. Sex differences in hippocampal long-term potentiation (LTP) and Pavlovian fear conditioning in rats: positive correlation between LTP and contextual learning. Brain Res. 1994; 661(1-2) : 25 -34 [PubMed]

  • 21.

    Baker F. Encyclopedia of Sleep. 2013; : 104 -7

  • 22.

    Paul KN, Dugovic C, Turek FW, Laposky AD. Diurnal sex differences in the sleep-wake cycle of mice are dependent on gonadal function. Sleep. 2006; 29(9) : 1211 -23 [PubMed]

  • 23.

    Kramar EA, Babayan AH, Gall CM, Lynch G. Estrogen promotes learning-related plasticity by modifying the synaptic cytoskeleton. Neuroscience. 2013; 239 : 3 -16 [DOI][PubMed]

  • 24.

    Wise PM. Estrogens and neuroprotection. Trends Endocrinol Metab. 2002; 13(6) : 229 -30 [PubMed]

  • 25.

    Manber R, Armitage R. Sex, steroids, and sleep: a review. Sleep. 1999; 22(5) : 540 -55 [PubMed]

  • 26.

    Alhola P, Tallus M, Kylmala M, Portin R, Polo-Kantola P. Sleep deprivation, cognitive performance, and hormone therapy in postmenopausal women. Menopause. 2005; 12(2) : 149 -55 [PubMed]

  • 27.

    Manson JE, Martin KA. Clinical practice. Postmenopausal hormone-replacement therapy. N Engl J Med. 2001; 345(1) : 34 -40 [DOI][PubMed]

  • 28.

    Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 2002; 25(6) : 295 -301 [PubMed]

  • 29.

    Jin J, Jing H, Choi G, Oh MS, Ryu JH, Jeong JW, et al. Voluntary exercise increases the new cell formation in the hippocampus of ovariectomized mice. Neurosci Lett. 2008; 439(3) : 260 -3 [DOI][PubMed]

  • 30.

    Vaynman S, Ying Z, Gomez-Pinilla F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci. 2004; 20(10) : 2580 -90 [DOI][PubMed]

  • 31.

    Ben J, Soares FM, Scherer EB, Cechetti F, Netto CA, Wyse AT. Running exercise effects on spatial and avoidance tasks in ovariectomized rats. Neurobiol Learn Mem. 2010; 94(3) : 312 -7 [DOI][PubMed]

  • 32.

    Stickgold R, Walker MP. Sleep-dependent memory consolidation and reconsolidation. Sleep Med. 2007; 8(4) : 331 -43 [DOI][PubMed]

  • 33.

    Walker MP, Stickgold R. Sleep-dependent learning and memory consolidation. Neuron. 2004; 44(1) : 121 -33 [DOI][PubMed]

  • 34.

    Machado RB, Hipolide DC, Benedito-Silva AA, Tufik S. Sleep deprivation induced by the modified multiple platform technique: quantification of sleep loss and recovery. Brain Res. 2004; 1004(1-2) : 45 -51 [DOI][PubMed]

  • 35.

    Suchecki D, Tufik S. Social stability attenuates the stress in the modified multiple platform method for paradoxical sleep deprivation in the rat. Physiol Behav. 2000; 68(3) : 309 -16 [PubMed]

  • 36.

    Zagaar M. Regular treadmill exercise prevents sleep deprivation-induced impairment of hippocampal-dependent memory and synaptic plasticity. 2011;

  • 37.

    McDermott CM, Hardy MN, Bazan NG, Magee JC. Sleep deprivation-induced alterations in excitatory synaptic transmission in the CA1 region of the rat hippocampus. J Physiol. 2006; 570(Pt 3) : 553 -65 [DOI][PubMed]

  • 38.

    Pilcher JJ, Huffcutt AI. Effects of sleep deprivation on performance: a meta-analysis. Sleep. 1996; 19(4) : 318 -26 [PubMed]

  • 39.

    Alvarenga TA, Patti CL, Andersen ML, Silva RH, Calzavara MB, Lopez GB, et al. Paradoxical sleep deprivation impairs acquisition, consolidation, and retrieval of a discriminative avoidance task in rats. Neurobiol Learn Mem. 2008; 90(4) : 624 -32 [DOI][PubMed]

  • 40.

    Ravassard P, Pachoud B, Comte JC, Mejia-Perez C, Scote-Blachon C, Gay N, et al. Paradoxical (REM) sleep deprivation causes a large and rapidly reversible decrease in long-term potentiation, synaptic transmission, glutamate receptor protein levels, and ERK/MAPK activation in the dorsal hippocampus. Sleep. 2009; 32(2) : 227 -40 [PubMed]

  • 41.

    Sherwin BB, Henry JF. Brain aging modulates the neuroprotective effects of estrogen on selective aspects of cognition in women: a critical review. Front Neuroendocrinol. 2008; 29(1) : 88 -113 [DOI][PubMed]

  • 42.

    Dzaja A, Arber S, Hislop J, Kerkhofs M, Kopp C, Pollmacher T, et al. Women's sleep in health and disease. J Psychiatr Res. 2005; 39(1) : 55 -76 [DOI][PubMed]

  • 43.

    Hogervorst E, Williams J, Budge M, Riedel W, Jolles J. The nature of the effect of female gonadal hormone replacement therapy on cognitive function in post-menopausal women: a meta-analysis. Neuroscience. 2000; 101(3) : 485 -512 [PubMed]

  • 44.

    Pike CJ, Carroll JC, Rosario ER, Barron AM. Protective actions of sex steroid hormones in Alzheimer's disease. Front Neuroendocrinol. 2009; 30(2) : 239 -58 [DOI][PubMed]

  • 45.

    Chen C, Hardy M, Zhang J, LaHoste GJ, Bazan NG. Altered NMDA receptor trafficking contributes to sleep deprivation-induced hippocampal synaptic and cognitive impairments. Biochem Biophys Res Commun. 2006; 340(2) : 435 -40 [DOI][PubMed]

  • 46.

    Alhaider IA, Aleisa AM, Tran TT, Alkadhi KA. Caffeine prevents sleep loss-induced deficits in long-term potentiation and related signaling molecules in the dentate gyrus. Eur J Neurosci. 2010; 31(8) : 1368 -76 [DOI][PubMed]

  • 47.

    Guan Z, Peng X, Fang J. Sleep deprivation impairs spatial memory and decreases extracellular signal-regulated kinase phosphorylation in the hippocampus. Brain Res. 2004; 1018(1) : 38 -47 [DOI][PubMed]

  • 48.

    Zagaar M, Dao A, Alhaider I, Alkadhi K. Regular treadmill exercise prevents sleep deprivation-induced disruption of synaptic plasticity and associated signaling cascade in the dentate gyrus. Mol Cell Neurosci. 2013; 56 : 375 -83 [DOI][PubMed]

  • 49.

    Goldman SE, Stone KL, Ancoli-Israel S, Blackwell T, Ewing SK, Boudreau R, et al. Poor sleep is associated with poorer physical performance and greater functional limitations in older women. Sleep. 2007; 30(10) : 1317 -24 [PubMed]

  • 50.

    Blackwell T, Yaffe K, Ancoli-Israel S, Schneider JL, Cauley JA, Hillier TA, et al. Poor sleep is associated with impaired cognitive function in older women: the study of osteoporotic fractures. J Gerontol A Biol Sci Med Sci. 2006; 61(4) : 405 -10 [PubMed]

  • 51.

    Woolley CS, McEwen BS. Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat. J Comp Neurol. 1993; 336(2) : 293 -306 [DOI][PubMed]

  • 52.

    Scharfman HE, Mercurio TC, Goodman JH, Wilson MA, MacLusky NJ. Hippocampal excitability increases during the estrous cycle in the rat: a potential role for brain-derived neurotrophic factor. J Neurosci. 2003; 23(37) : 11641 -52 [PubMed]

  • 53.

    Scharfman HE, MacLusky NJ. Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: complexity of steroid hormone-growth factor interactions in the adult CNS. Front Neuroendocrinol. 2006; 27(4) : 415 -35 [DOI][PubMed]

  • 54.

    Scharfman HE, Maclusky NJ. Similarities between actions of estrogen and BDNF in the hippocampus: coincidence or clue? Trends Neurosci. 2005; 28(2) : 79 -85 [DOI][PubMed]

  • 55.

    Zagaar M, Dao A, Levine A, Alhaider I, Alkadhi K. Regular exercise prevents sleep deprivation associated impairment of long-term memory and synaptic plasticity in the CA1 area of the hippocampus. Sleep. 2013; 36(5) : 751 -61 [DOI][PubMed]

  • 56.

    Hajali V, Sheibani V, Esmaeili-Mahani S, Shabani M. Female rats are more susceptible to the deleterious effects of paradoxical sleep deprivation on cognitive performance. Behav Brain Res. 2012; 228(2) : 311 -8 [DOI][PubMed]

  • 57.

    Pietrelli A, Lopez-Costa J, Goni R, Brusco A, Basso N. Aerobic exercise prevents age-dependent cognitive decline and reduces anxiety-related behaviors in middle-aged and old rats. Neuroscience. 2012; 202 : 252 -66 [DOI][PubMed]

  • 58.

    Liu HL, Zhao G, Cai K, Zhao HH, Shi LD. Treadmill exercise prevents decline in spatial learning and memory in APP/PS1 transgenic mice through improvement of hippocampal long-term potentiation. Behav Brain Res. 2011; 218(2) : 308 -14 [DOI][PubMed]

  • 59.

    Radak Z, Hart N, Sarga L, Koltai E, Atalay M, Ohno H, et al. Exercise plays a preventive role against Alzheimer's disease. J Alzheimers Dis. 2010; 20(3) : 777 -83 [DOI][PubMed]

  • 60.

    Ding YH, Luan XD, Li J, Rafols JA, Guthinkonda M, Diaz FG, et al. Exercise-induced overexpression of angiogenic factors and reduction of ischemia/reperfusion injury in stroke. Curr Neurovasc Res. 2004; 1(5) : 411 -20 [PubMed]

  • 61.

    Aguiar AJ, Castro AA, Moreira EL, Glaser V, Santos AR, Tasca CI, et al. Short bouts of mild-intensity physical exercise improve spatial learning and memory in aging rats: involvement of hippocampal plasticity via AKT, CREB and BDNF signaling. Mech Ageing Dev. 2011; 132(11-12) : 560 -7 [DOI][PubMed]

  • 62.

    Berchtold NC, Castello N, Cotman CW. Exercise and time-dependent benefits to learning and memory. Neuroscience. 2010; 167(3) : 588 -97 [DOI][PubMed]

  • 63.

    Lin TW, Chen SJ, Huang TY, Chang CY, Chuang JI, Wu FS, et al. Different types of exercise induce differential effects on neuronal adaptations and memory performance. Neurobiol Learn Mem. 2012; 97(1) : 140 -7 [DOI][PubMed]

  • 64.

    O'Callaghan RM, Ohle R, Kelly AM. The effects of forced exercise on hippocampal plasticity in the rat: A comparison of LTP, spatial- and non-spatial learning. Behav Brain Res. 2007; 176(2) : 362 -6 [DOI][PubMed]

  • 65.

    van Praag H, Christie BR, Sejnowski TJ, Gage FH. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci U S A. 1999; 96(23) : 13427 -31 [PubMed]

  • 66.

    Ang ET, Gomez-Pinilla F. Potential therapeutic effects of exercise to the brain. Curr Med Chem. 2007; 14(24) : 2564 -71 [PubMed]

  • 67.

    Leasure JL, Jones M. Forced and voluntary exercise differentially affect brain and behavior. Neuroscience. 2008; 156(3) : 456 -65 [DOI][PubMed]

  • 68.

    Saadati H, Babri S, Ahmadiasl N, Mashhadi M. Effects of exercise on memory consolidation and retrieval of passive avoidance learning in young male rats. Asian J Sports Med. 2010; 1(3) : 137 -42 [PubMed]

  • 69.

    Titterness AK, Wiebe E, Kwasnica A, Keyes G, Christie BR. Voluntary exercise does not enhance long-term potentiation in the adolescent female dentate gyrus. Neuroscience. 2011; 183 : 25 -31 [DOI][PubMed]

  • 70.

    LeBlanc ES, Janowsky J, Chan BK, Nelson HD. Hormone replacement therapy and cognition: systematic review and meta-analysis. JAMA. 2001; 285(11) : 1489 -99 [PubMed]

  • 71.

    Zandi PP, Carlson MC, Plassman BL, Welsh-Bohmer KA, Mayer LS, Steffens DC, et al. Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study. JAMA. 2002; 288(17) : 2123 -9 [PubMed]

  • 72.

    Jahangard L, Haghighi M, Bajoghli H, Holsboer-Trachsler E, Brand S. Among a sample of Iranian premenopausal and menopausal women differences in mood, sleep and health quality are small. Int J Psychiatry Clin Pract. 2014; 18(2) : 139 -44 [DOI][PubMed]

  • 73.

    Mattson MP, Maudsley S, Martin B. BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends Neurosci. 2004; 27(10) : 589 -94 [DOI][PubMed]

  • 74.

    Berchtold NC, Kesslak JP, Pike CJ, Adlard PA, Cotman CW. Estrogen and exercise interact to regulate brain-derived neurotrophic factor mRNA and protein expression in the hippocampus. Eur J Neurosci. 2001; 14(12) : 1992 -2002 [PubMed]

  • 75.

    Bechara RG, Lyne R, Kelly AM. BDNF-stimulated intracellular signalling mechanisms underlie exercise-induced improvement in spatial memory in the male Wistar rat. Behav Brain Res. 2014; 275 : 297 -306 [DOI][PubMed]

  • 76.

    Tyler WJ, Alonso M, Bramham CR, Pozzo-Miller LD. From acquisition to consolidation: on the role of brain-derived neurotrophic factor signaling in hippocampal-dependent learning. Learn Mem. 2002; 9(5) : 224 -37 [DOI][PubMed]

  • 77.

    Pelleymounter MA, Cullen MJ, Baker MB, Gollub M, Wellman C. The effects of intrahippocampal BDNF and NGF on spatial learning in aged Long Evans rats. Mol Chem Neuropathol. 1996; 29(2-3) : 211 -26 [DOI][PubMed]

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