Corticosterone injection into the basolateral amygdala before and after memory reactivation impairs the subsequent expression of fear memory in rats: An interaction of glucocorticoids and ß-adrenoceptors.

Glucocorticoid administration, before or after fear memory reactivation, impairs subsequent fear memory expression, but the underlying mechanisms are not well understood. The present study examined the role of basolateral amygdala (BLA) ß-adrenoceptors in the effects of intra-BLA corticosterone injection on fear memory in rats. Bilateral cannulae were implanted in the BLA of Wistar male rats. The rats were trained and tested using an inhibitory avoidance task (1 mA footshock for 3 s). Forty-eight hours after training, corticosterone (CORT, 5, 10, or 20 ng/0.5 µl/side) and the ß2-adrenoceptor agonist clenbuterol (CLEN, 10 or 20 ng/0.5 µl/side) or the ß-adrenoceptor antagonist propranolol (PROP, 250 or 500 ng/0.5 µl/side) were injected into the BLA before or right after memory reactivation (retrieval, Test 1). We performed subsequent tests 2 (Test 2), 5 (Test 3), 7 (Test 4), and 9 (Test 5) days after Test 1. The results demonstrated that CORT injection before Test 1 disrupted memory retrieval and reduced fear expression in Tests 2-5, possibly due to enhanced extinction or impaired reconsolidation. CORT injection after Test 1 also impaired reconsolidation and reduced fear expression in Tests 2-5. CLEN prevented, but PROP exacerbated, the effects of CORT on fear expression. The reminder shock did not recover fear memory in CORT-treated animals, suggesting that reconsolidation, not extinction, was affected. These results indicate that glucocorticoids and ß-adrenoceptors in the BLA jointly modulate fear memory reconsolidation and expression. Comprehending the neurobiology of stress and the impact of glucocorticoids on fear memory may lead to new treatments for stress and trauma-induced disorders such as PTSD.

Systemic corticosterone administration impairs the late fear memory reconsolidation via basolateral amygdala glucocorticoid receptors: Dependence on the time window and memory age.

Glucocorticoid receptors (GRs) of the basolateral amygdala (BLA) play an important role in memory reconsolidation. The present study investigated the role of the BLA GRs in the late reconsolidation of fear memory using an inhibitory avoidance (IA) task in male Wistar rats. Stainless steel cannulae were implanted bilaterally into the BLA of the rats. After 7 days of recovery, the animals were trained in a one-trial IA task (1 mA, 3 s). In Experiment One, 48 h after the training session, the animals received 3 systemic doses of corticosterone (CORT; 1, 3, or 10 mg/kg, i.p.) followed by an intra-BLA microinjection of the vehicle (0.3 µl/side) at different time points (immediately, 12, or 24 h) after memory reactivation. Memory reactivation was performed by returning the animals to the light compartment while the sliding door was open. No shock was delivered during memory reactivation. CORT (10 mg/kg) injection 12 h after memory reactivation most effectively impaired the late memory reconsolidation (LMR). In the second part of Experiment One, immediately, 12, or 24 h after memory reactivation, GR antagonist RU38486 (RU; 1 ng/0.3 µl/side) was injected into BLA following a systemic injection of CORT (10 mg/kg) to examine whether it would block the CORT effect. RU inhibited the impairing effects of CORT on LMR. In Experiment Two, the animals received CORT (10 mg/kg) with time windows immediately, 3, 6, 12, and 24 h after memory reactivation. Again, CORT (10 mg/kg) injection 12 h after memory reactivation impaired LMR. Memory reactivation was performed in the third Experiment, 7, 14, 28, or 56 days after the training session. Injection of CORT (10 mg/kg) 12 h later had no significant effect on the LMR. The impairing effect of CORT was seen only in 2-day-old but not 7, 14, 28, and 56-day-old memories. GRs located in BLA seem to play an important role in the LMR of young memory, as with increasing the age of memories, they become less sensitive to manipulation.

EMF promote BMSCs differentiation and functional recovery in hemiparkinsonian rats.

Bone marrow mesenchymal stem cells (BMSCs) have self-renewal ability while maintaining the proliferation facility. The BMSCs reproducing ability could affect by electromagnetic fields (EMFs) as a physical inducing factor. We focused on the EMF (400 µT, 75 Hz) exposed multi-potential BMSCs which differentiated and successfully implanted in the substantia nigra pars compacta (SNpc) of Parkinson's disease rat model. The purified BMSCs are exposed to sinusoidal and square waveform EMF (1 h/1 week or 7 h/1 day) then injected into the left SNpc of Parkinson's rats. To evaluate the morphology of EMF exposed BMSCs, the cresyl violet staining labeled the Nissl bodies. After evaluation of the rat's activity by behavioral tests (open-field and rotarod tests), the brains were obtained for the preparation of SNpc blocks and carry out the cresyl violet staining. Cell morphology proved most cell differentiation to neurons in the sinusoidal EMF groups. In the sinusoidal EMF exposure groups, large and small neurons were seen with apparent synapses. Although in the square EMF exposed groups some neurons were seen, most of the differentiated cells were astrocytes, microglia, and oligodendrocyte. The results confirmed an improvement in locomotors' activity of BMSC alone and sinusoidal EMF exposed groups. We presented a low-frequency EMF (75 Hz) to promote the capability of BMSC proliferation, differentiation to neurons and glial cells, and motor coordination activity in the treatment of hemiparkinsonian rats.

Exercise and crocin prevent adolescent-stress induced impairment of spatial navigation and dendritic retraction in the hippocampal CA3 area in adult male rats.

Adolescent chronic stress has been shown to induce functional, biochemical and morphological modifications of the hippocampus, leading to stress-related disorders in adulthood. The present study investigated the effects of exercise, crocin and their combination on spatial learning and memory impairment and dendritic retraction of the CA3 pyramidal neurons induced by chronic adolescent stress in adult male rats. Rats were exposed to restraint stress 2 h/day for 10 days during postnatal days (PNDs) 30-40. Following this period, separate groups of animals were treated with crocin (25 and 50 mg/kg), exposed to running wheel, and or received the combined treatment during PNDs 41-55. Following the interventions, plasma levels of corticosterone, spatial learning and memory, apical dendritic length of CA3 pyramidal neurons and BDNF levels in the CA3 area were assessed. Findings showed that adolescent stress significantly increased corticosterone levels and caused a tendency to reduce CA3 BDNF levels. Adolescent stress also impaired spatial learning and memory, and retracted apical dendritic length of CA3 pyramidal neurons. Crocin, voluntary exercise, and their combination recovered stress-induced spatial learning and impairment and CA3 pyramidal neurons dendritic length retraction. All treatments also reduced significantly corticosterone levels and enhanced CA3 BDNF levels in the stress groups. Finally, these treatments even increased apical dendritic length of CA3 pyramidal neurons in the non-stress groups. These findings indicate that detrimental effects of adolescent stress on cognitive function and hippocampal morphology in adulthood could be restored by early interventions with physical activity and crocin treatment during adolescent period.