Impairment Of Spatial Learning Ability Research Articles

Fluoxetine attenuates the impairment of spatial learning ability and prevents neuron loss in middle-aged APPswe/PSEN1dE9 double transgenic Alzheimer's disease mice.

Selective serotonin reuptake inhibitors (SSRIs) have been reported to increase cognitive performance in some clinical studies of Alzheimer’s disease (AD). However, there is a lack of evidence supporting the efficacy of SSRIs as cognition enhancers in AD, and the role of SSRIs as a treatment for AD remains largely unclear. Here, we characterized the impact of fluoxetine (FLX), a well-known SSRI, on neurons in the dentate gyrus (DG) and in CA1 and CA3 of the hippocampus of middle-aged (16 to 17 months old) APPswe/PSEN1dE9 (APP/PS1) transgenic AD model mice. We found that intraperitoneal (i.p.) injection of FLX (10 mg/kg/day) for 5 weeks effectively alleviated the impairment of spatial learning ability in middle-aged APP/PS1 mice as evaluated using the Morris water maze. More importantly, the number of neurons in the hippocampal DG was significantly increased by FLX. Additionally, FLX reduced the deposition of beta amyloid, inhibited GSK-3β activity and increased the level of β-catenin in middle-aged APP/PS1 mice. Collectively, the results of this study indicate that FLX delayed the progression of neuronal loss in the hippocampal DG in middle-aged AD mice, and this effect may underlie the FLX-induced improvement in learning ability. FLX may therefore serve as a promising therapeutic drug for AD.

Treadmill exercise improves spatial learning ability by enhancing brain-derived neurotrophic factor expression in the attention-deficit/hyperactivity disorder rats.

Attention-deficit/hyperactivity disorder (ADHD) patients show learning difficulty and impulsiveness. Exercise is known to improve learning ability and memory function. In the present study, we investigated the duration-dependence of the effect of treadmill exercise on spatial learning ability in relation with brain-derived neurotrophic factor (BDNF) expression in ADHD rats. For this study, radial 8-arm maze test and western blot for BDNF and tyrosine kinase B (TrkB) were performed. Spontaneous hypertensive rats were used as the ADHD rats and Wistar-Kyoto rats were used as the control rats. The rats in the exercise groups were forced to run on a treadmill for 10 min, 30 min, and 60 min once a day for 28 consecutive days. ADHD rats displayed impairment of spatial learning ability, in contrast treadmill exercise ameliorated impairment of spatial learning ability. Treadmill exercise for 30 min per day showed most potent ameliorating effect on impairment of spatial learning ability. BDNF and TrkB expressions in the hippocampus were decreased in the ADHD rats, in contrast treadmill exercise enhanced BDNF and TrkB expressions. Treadmill exercise for 30 min and for 60 min per day showed enhancing effects on BDNF and TrkB expressions. Treadmill exercise alleviated deficits in the spatial learning ability through enhancing BDNF and TrkB expressions in the ADHD rats. Treadmill exercise for 30 min per day can be considered as the most effective therapeutic modality for the ADHD symptoms.

Treadmill exercise alleviates impairment of spatial learning ability through enhancing cell proliferation in the streptozotocin-induced Alzheimer's disease rats.

Alzheimer’s disease is the most common cause of dementia. This disease is a progressive and irreversible brain disorder accompanied with severe learning and memory impairment. Exercise increases cognitive ability, attenuates motor deficits, increases new neuron formation, and ameliorates neurological impairments in several neurodegenerative diseases. This study investigated the effects of treadmill exercise on spatial learning ability in relation with cell proliferation in the hippocampus. The rat model of Alzheimer’s disease was induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) using a stereotaxic instrument. The rats in the exercise groups were forced to run on a treadmill for once 30 min daily for 28 consecutive days starting at 3 days after the ICV injection of STZ. Radial 8-arm maze test was conducted for the spatial learning ability. New neuron formation in the hippocampus was detected by 5-bromo-2’-deoxyuridine (BrdU) immunohistochemistry. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions were examined by western blot analysis. The present results show that ICV injection of STZ impaired spatial learning ability. Decreased cell proliferation with decrement of BDNF and TrkB expressions in the hippocampus were observed in the STZ-induced Alzheimer’s disease rats. However, treadmill exercise alleviated deficits of spatial learning ability. Treadmill exercise enhanced cell proliferation and increased BDNF and TrkB expressions in the rats with ICV injection of STZ. The present study suggests that treadmill exercise can be a useful strategy for treating memory impairment induced by several neurodegenerative diseases.

Treadmill exercise alleviates prenatal noise stress-induced impairment of spatial learning ability through enhancing hippocampal neurogenesis in rat pups

Stress alters brain cell properties and then disturbs cognitive processes, such as learning and memory. In this study, we investigated the effect of postnatal treadmill exercise on hippocampal neurogenesis and spatial learning ability of rat pups following prenatal noise stress. The impact of exercise intensity (mild-intensity exercise vs heavy-intensity exercise) was also compared. The pregnant rats in the stress-applied group were exposed to a 95 dB supersonic machine sound for 1 h once a day from the 15th day after mating until delivery. After birth, the rat pups in the exercise groups were made to run on a treadmill for 30 min once a day for 7 consecutive days, starting 4 weeks after birth. The spatial learning ability was tested using radial-arm maze task and hippocampal neurogenesis was determined by 5-bromo-2′-deoxyuridine (BrdU) immunohistochemistry. The rat pups born from the stress-applied maternal rats spent more time for the seeking of water and showed higher number of error in the radial-arm maze task compared to the control group. These rat pups showed suppressed neurogenesis in the hippocampus. In contrast, the rat pups performed postnatal treadmill exercise saved time for seeking of water and showed lower number of error compared to the stress-applied group. Postnatal treadmill exercise also enhanced neurogenesis in the hippocampus. The mild-intensity exercise showed more potent impact compared to the heavy-intensity exercise. The present results reveal that postnatal treadmill exercise lessens prenatal stress-induced deterioration of brain function in offspring.

Treadmill exercise ameliorates impairment of spatial learning ability through enhancing dopamine expression in hypoxic ischemia brain injury in neonatal rats

Substantia nigra and striatum are vulnerable to hypoxic ischemia brain injury. Physical exercise promotes cell survival and functional recovery after brain injury. However, the effects of treadmill exercise on nigro-striatal dopaminergic neuronal loss induced by hypoxic ischemia brain injury in neonatal stage are largely unknown. We determined the effects of treadmill exercise on survival of dopamine neurons in the substantia nigra and dopaminergic fibers in the striatum after hypoxic ischemia brain injury. On postnatal 7 day, left common carotid artery of the neonatal rats ligated for two hours and the neonatal rats were exposed to hypoxia conditions for one hour. The rat pups in the exercise groups were forced to run on a motorized treadmill for 30 min once a day for 12 weeks, starting 22 days after induction of hypoxic ischemia brain injury. Spatial learning ability in rat pups was determined by Morris water maze test after last treadmill exercise. The viability of dopamine neurons in the substantia nigra and dopamine fibers in the striatum were analyzed using immunohistochemistry. In this study, hypoxic ischemia injury caused loss of dopamine neurons in the substantia nigra and dopaminergic fibers in the striatum. Induction of hypoxic ischemia deteriorated spatial learning ability. Treadmill exercise ameliorated nigro-striatal dopaminergic neuronal loss, resulting in the improvement of spatial learning ability. The present study suggests the possibility that treadmill exercise in early adolescent period may provide a useful strategy for the recovery after neonatal hypoxic ischemia brain injury.

Reduced thyroid hormones with increased hippocampal SNAP-25 and Munc18-1 might involve cognitive impairment during aging

The mechanism underlying the decline of age-related learning and memory remains unclear. Brain-region-specific changes of synaptic proteins and decreased thyroid hormones (THs) have been implied involving this decline. During normal aging, however, the relationships among synaptic proteins, THs and abilities of learning and memory remain to be elucidated. In this study, the age-related spatial learning and memory ability of 41 Kunming mice (KM) (14 mice aged 6 months, 13 mice aged 11 months, 14 mice aged 22 months) was measured with radial six-arm water maze. The levels of SNAP-25 and Munc18-1 in brain regions were semi-quantified by Western blotting and the serum THs were detected by radioimmunoassay. Our results showed the old Kunming mice had marked impairment of spatial learning and memory, with decreased serum free triiodothyronine (FT3) and increased SNAP-25 and Munc18-1 in dorsal hippocampus (DH), ventral hippocampus (VH) and frontal lobe (F). The Pearson's correlation test showed the impairment of spatial learning ability positively correlated with SNAP-25 in DH and Munc18-1 in DH and VH. While, the levels of SNAP-25 (DH, VH and F) and Munc18-1 (DH) negatively correlated with the serum FT3 level, and the spatial memory decline marginal negatively correlate with serum THs. These results suggested that increased hippocampal SNAP-25 and Munc18-1 which seemingly result from decreased serum THs might involve the age-related impairment of spatial learning and memory.