High-intensity interval training improves long-term memory and increases hippocampal antioxidant activity and BDNF levels in ovariectomized Wistar rats.

Menopause is the period in which women cease to produce the hormone estrogen, which can trigger physiological, cognitive, and behavioral changes. In this context, alternatives are needed that can reduce the effects provided by menopause, specifically in terms of cognitive and behavioral aspects. High-intensity interval training (HIIT) is an exercise protocol that has shown the potential to improve cognition by promoting an increase in antioxidant defenses and BDNF levels. Therefore, the aim of this study was to evaluate the effects of HIIT on behavior and hippocampal neurochemistry in ovariectomized adult rats. Four groups of rats were divided into: females without ovariectomy surgery and sedentary (SHAM-SED); females with ovariectomy surgery and sedentary (OVX-SED); females without ovariectomy surgery and trained (SHAM-HIIT); females with ovariectomy surgery and trained (OVX-HIIT). After the surgical procedure and the HIIT protocol, the animals underwent anxiety (elevated plus maze and open field) and memory (novel object recognition) tests. Corticosterone was measured in blood and BDNF levels and redox status were evaluated in the hippocampus. The OVX-SED group showed low BDNF levels and antioxidant enzymes, which may be linked to the observed memory impairments. The HIIT protocol (SHAM-HIIT and OVX-HIIT groups) increased the BDNF levels and antioxidant enzymes in the hippocampus, improving the animals' memory. However, HIIT also led to increased plasma corticosterone and anxiety-like behaviors. The ovariectomy procedure induced memory impairment probably due to reductions in hippocampal BDNF levels and redox imbalance. The HIIT protocol demonstrates promising results as an alternative to improve memory in ovariectomized rats.

Angiotensin-(1-7)/Mas axis modulates fear memory and extinction in mice.

Inappropriate defense-alerting reaction to fear is a common feature of neuropsychiatric diseases. Therefore, impairments in brain circuits, as well as in molecular pathways underlying the neurovegetative adjustments to fear may play an essential role on developing neuropsychiatric disorders. Here we tested the hypothesis that interfering with angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis homeostasis, which appears to be essential to arterial pressure control, would affect fear memory and extinction. Mas knockout (MasKO) mice, in FVB/N background, showed normal cued fear memory and extinction, but increased freezing in response to context. Next, as FVB/N has poor performance in contextual fear memory, we tested MasKO in mixed 129xC57BL/6 background. MasKO mice behaved similarly to wild-type (WT), but memory extinction was slower in contextual fear conditioning to a weak protocol (1CS/US). In addition, delayed extinction in MasKO mice was even more pronounced after a stronger protocol (3CS/US). We showed previously that Angiotensin II receptor AT1 antagonist, losantan, rescued object recognition memory deficit in MasKO mice. Here, losartan was also effective. Memory extinction was accelerated in MasKO mice after treatment with losartan. In conclusion, we showed for the first time that Ang-(1-7)/Mas axis may modulate fear memory extinction. Furthermore, we suggest MasKO mice as an animal model to study post-traumatic stress disorder (PTSD).

Temporal rearrangement of pre-ictal PTZ induced spike discharges by low frequency electrical stimulation to the amygdaloid complex.

BACKGROUND: Epilepsy is a common neurological disease affecting over 40 million people worldwide. The foremost important challenge of epileptologists has been to control and predict the recurrent and spontaneous seizures of epileptic patients. The application of low frequency electrical stimulation (LFS) in deep brain structures has shown promising results in seizure control. However, the use of LFS as a probing strategy for seizure prediction, thus contributing to a closed loop solution, is still poorly explored. OBJECTIVE: To improve seizure prediction by producing gradually increasing phase-locked pre-ictal electrographical responses, due to the short-term plastic changes in epileptogenic neural networks, thus behaving as a "programmed" surrogate marker. METHODS: Urethane anesthetized rats were divided into 3 groups: the PTZ-noES group was injected with pentylenetetrazole (PTZ 4 mg/ml/min flow rate) i.v. without electrical stimulation (ES); the ES-noPTZ group received ES (0.5 Hz, 0.1 ms pulse width and 0.6 mA) to the amygdaloid complex and the PTZ + ES group received simultaneously i.v. PTZ infusion and ES. After each condition, electrographical parameters and c-Fos expression of regions of interest were evaluated. RESULTS: Although the PTZ + ES group had no evident change in the sustained electrographic seizure onset, duration and/or frequency spectrum; c-Fos labeling showed a different expression pattern when compared to the PTZ-noES and ES-noPTZ. Also, PTZ + ES formed a gradually increasing evoked potential; confirming the strong coupling of reverberant neural networks induced by ES - phase locked to stimuli. CONCLUSION: ES induces a detectable temporal rearrangement of pre-ictal activity, which has suggestive applicability to seizure prediction.