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Numerous observations in clinical and preclinical studies indicate that the developing brain is particular sensitive to lead (Pb)''s pernicious effects. However, the effect of gestation-only Pb exposure on cognitive functions at maturation has not been studied. We investigated the potential effects of three levels of Pb exposure (low, middle, and high Pb: 0.03%, 0.09%, and 0.27% of lead acetate-containing diets) at the gestational period on the spatial memory of young adult offspring by Morris water maze spatial learning and fixed location/visible platform tasks. Our results revealed that three levels of Pb exposure significantly impaired memory retrieval in male offspring, but only female offspring at low levels of Pb exposure showed impairment of memory retrieval. These impairments were not due to the gross disturbances in motor performance and in vision because these animals performed the fixed location/visible platform task as well as controls, indicating that the specific aspects of spatial learning/memory were impaired. These results suggest that exposure to Pb during the gestational period is sufficient to cause long-term learning/memory deficits in young adult offspring. [Copyright &y& Elsevier]

Behavioral stress can either block or facilitate memory and affect the induction of long-term potentiation (LTP) and long-term depression (LTD). However, the relevance of the stress experience-dependent long-term depression (SLTD) to spatial memory task is unknown. Here we have investigated the effects of acute and sub-acute elevated platform (EP) and foot shock (FS) stress on LTD induction in CA1 region of the hippocampus of anesthetized rats and spatial memory in Morris water maze. We found that LTD was facilitated by acute EP stress, but not by sub-acute EP stress that may be due to the fast adaptation of the animals to this naturalistic mild stress. However, FS stress, an inadaptable strong stress, facilitated LTD induction both in acute and sub-acute treatment. In addition, with the same stress protocols, acute EP stress impaired spatial memory but the sub-acute EP stressed animals performed the spatial memory task as well as the controls, may due to the same reason of adaptation. However, acute FS stress slightly impaired learning but sub-acute FS even enhanced memory retrieval. Our results showed that SLTD was disassociated with the effect of stress on memory task but might be related to stress experience-dependent form of aberrant memory. [Copyright &y& Elsevier]

Promoting extinction of fear memory is the main treatment of fear disorders, especially post-traumatic stress disorder (PTSD). However, fear extinction is often incomplete in these patients. Our previous study had shown that Rac1 activity in hippocampus plays a crucial role in the learning of contextual fear memory in rats. Here, we further investigated whether Rac1 activity also modulated the extinction of contextual fear memory. We found that massed extinction obviously upregulated hippocampal Rac1 activity and induced long-term extinction of contextual fear in rats. Intrahippocampal injection of the Rac1 inhibitor NSC23766 prevents extinction of contextual fear in massed extinction training rats. In contrast, long-spaced extinction downregulated Rac1 activity and caused less extinction. And Rac1 activator CN04-A promotes extinction of contextual fear in long-spaced extinction rats. Our study demonstrates that inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear, suggesting that modulating Rac1 activity of the hippocampus may be promising therapy of fear disorders. [ABSTRACT FROM AUTHOR]

Thyroid hormone disorders have long been linked to depression, but the causal relationship between them remains controversial. To address this question, we established rat models of hypothyroidism using 131 iodine ( 131 I) and hyperthyroidism using levothyroxine (LT 4 ). Serum free thyroxine (FT 4 ) and triiodothyronine (FT 3 ) significantly decreased in the hypothyroid of rats with single injections of 131 I (5 mCi/kg). These rats exhibited decreased depression-like behaviors in forced swimming test and sucrose preference tests, as well as decreased anxiety-like behaviors in an elevated plus maze. Diminished levels of brain serotonin (5-HT) and increased levels of hippocampal brain-derived neurotrophic factor (BDNF) were found in the hypothyroid rats compared to the control saline–vehicle administered rats. LT 4 treatment reversed the decrease in thyroid hormones and depression-like behaviors. In contrast, hyperthyroidism induced by weekly injections of LT 4 (15 μg/kg) caused a greater than 10-fold increase in serum FT 4 and FT 3 levels. The hyperthyroid rats exhibited higher anxiety- and depression-like behaviors, higher brain 5-HT level, and lower hippocampal BDNF levels than the controls. Treatment with the antidepressant imipramine (15 mg/kg) diminished serum FT 4 levels as well as anxiety- and depression-like behaviors in the hyperthyroid rats but led to a further increase in brain 5-HT levels, compared with the controls or the hypothyroid rats. Together, our results suggest that hypothyroidism and hyperthyroidism have bidirectional effects on anxiety- and depression-like behaviors in rats, possibly by modulating hippocampal BDNF levels. [ABSTRACT FROM AUTHOR]

• Microvascular density, length and diameter were reduced in the rat hippocampus upon aging. • Microglial and astrocyte were increased and their morphology have changed in the rat hippocampus upon aging. • Hippocampal PV and SST neurons were reduced upon aging and that SST neurons were lost earlier. • Impairment of hippocampal neuro-vascular unit is earlier than spatial cognition in normal aging rats. Ageing is the major risk factor for the most neurodegenerative diseases, such as Alzheimer's disease (AD). Damage to neurovascular components (microvessels, glia, and neurons) occurs with ageing and is suspected to exacerbate or cause mild cognitive impairment (MCI), vascular dementia, and AD. However, whether vascular cells, glia, and neurons change synchronously or asynchronously during ageing is unclear, and the relationship between complex dynamic pathophysiological changes in the brain and cognitive ability needs to be further studied. We used male Sprague–Dawley (SD) rats of three different ages (2 months, 12 months, and 24 months) and explored changes in the neurovascular unit (cerebral vessels, microglia, astrocytes, and neurons) and spatial memory upon normal ageing by the Morris water maze (MWM) test and immunofluorescence staining. We found that the impairments of microvessels, glia, neurons, and spatial memory were age-dependent in the rat hippocampus. In middle-aged (12-month-old) rats, some neurovascular unit components have become abnormal: the density and length of microvessels, pyramidal neuron, and SST (Somatostatin) neuron number was decreased, the number of astrocytes was increased in the hippocampus. The diameter of microvessels and PV (Parvalbumin) neuron numbers were decreased, the microglial number was increased and spatial learning was deficit at 24 months of age. In conclusion, we found that the impairment of the hippocampal neuro-vascular unit precedes changes in spatial cognition in naturally aged rats. [ABSTRACT FROM AUTHOR]

Chronic stress is the major cause of clinical depression. The behavioral signs of depression, including anhedonia, learning and memory deficits, and sleep disruption, result from the damaging effects of stress hormones on specific neural pathways. The Chinese tree shrew (Tupaia belangeri chinensis) is an aggressive non-human primate with a hierarchical social structure that has become a well-established model of the behavioral, endocrine, and neurobiological changes associated with stress-induced depression. The tricyclic antidepressant clomipramine treats many of the core symptoms of depression in humans. To further test the validity of the tree shrew model of depression, we examined the effects of clomipramine on depression-like behaviors and physiological stress responses induced by social defeat in subordinate tree shrews. Social defeat led to weight loss, anhedonia (as measured by sucrose preference), unstable fluctuations in locomotor activity, sustained urinary cortisol elevation, irregular cortisol rhythms, and deficient hippocampal long-term potentiation (LTP). Clomipramine ameliorated anhedonia and irregular locomotor activity, and partially rescued the irregular cortisol rhythm. In contrast, weight loss increased, cortisol levels were even higher, and in vitro LTP was still impaired in the clomipramine treatment group. These results demonstrate the unique advantage of the tree shrew social defeat model of depression. [ABSTRACT FROM AUTHOR]