Unraveling the Influence of Litter Size, Maternal Care, Exercise, and Aging on Neurobehavioral Plasticity and Dentate Gyrus Microglia Dynamics in Male Rats.

This study explores the multifaceted influence of litter size, maternal care, exercise, and aging on rats' neurobehavioral plasticity and dentate gyrus microglia dynamics. Body weight evolution revealed a progressive increase until maturity, followed by a decline during aging, with larger litters exhibiting lower weights initially. Notably, exercised rats from smaller litters displayed higher body weights during the mature and aged stages. The dentate gyrus volumes showed no significant differences among groups, except for aged sedentary rats from smaller litters, which exhibited a reduction. Maternal care varied significantly based on litter size, with large litter dams showing lower frequencies of caregiving behaviors. Behavioral assays highlighted the detrimental impact of a sedentary lifestyle and reduced maternal care/large litters on spatial memory, mitigated by exercise in aged rats from smaller litters. The microglial dynamics in the layers of dentate gyrus revealed age-related changes modulated by litter size and exercise. Exercise interventions mitigated microgliosis associated with aging, particularly in aged rats. These findings underscore the complex interplay between early-life experiences, exercise, microglial dynamics, and neurobehavioral outcomes during aging.

Responses Triggered by the Immune System in Hypertensive Conditions and Repercussions on Target Organ Damage: A Review.

BACKGROUND: Hypertension is a chronic, multifactorial clinical condition characterized by sustained high blood pressure levels. It is often associated with functional-structural alterations of target organs, which include heart, brain, kidneys, and vasculature. OBJECTIVE: This study highlights the recent correlation between the immune system and hypertension and its repercussions on target-organ damage. METHODS: The descriptors used for the search of the study were "hypertension", "immunity", and "target organs". The methodology of the study followed the main recommendations of the PRISMA statement. RESULTS: The damage to the vasculature arises mainly from the migration of T cells and monocytes that become pro-inflammatory in the adventitia, releasing TNF-α, IFN-γ, and IL-17, which induce endothelial damage and hinder vascular relaxation. In the renal context, the inflammatory process associated with hypertension culminates in renal invasion by leukocytes, which contribute to the injury of this organ by mechanisms of intense sympathetic stimulation, activation of the reninangiotensin system, sodium retention, and aggravation of oxidative stress. In the cardiac context, hypertension increases the expression of pro-inflammatory elements, such as B, T, and NK cells, in addition to the secretion of IFN-γ, IL-17, IL-23, and TNF-α from angiotensin II, reactive oxygen species, and aldosterone. This pro-inflammatory action is also involved in brain damage through SphK1. In view of the above, the participation of the immune system in hypertension-induced injuries seems to be unequivocal. CONCLUSION: Therefore, understanding the multifactorial mechanisms related to hypertension will certainly allow for more efficient interventions in this condition, preventing target organ damage.

Can coconut oil and treadmill exercise during the critical period of brain development ameliorate stress-related effects on anxiety-like behavior and episodic-like memory in young rats?

OBJECTIVE: Virgin coconut oil (CO) and treadmill exercise have been reported to improve memory performance in young rats. CO has also been associated with antistress properties in young, stressed mice. Therefore, in this study we aimed to investigate whether CO and treadmill exercise could synergistically ameliorate the effects of chronic stress on anxiety-like behavior and episodic-like memory in young rats. METHODS: The rats received CO and were exercised (Ex) from the 15th to the 45th day of life. The animals were supplemented with CO (10 mL kg-1 day-1) or a vehicle (V, distilled water and 0.009% Cremophor) via oral gavage. The Ex animals were placed for 30 min day-1 on a treadmill, with the speed gradually increasing from the first week to the last. From the 46th to the 54th postnatal day, with the exception of the 51st and the 52nd day, all rats were subjected to restraint stress. Afterwards, all rats underwent the open-field test to evaluate locomotor activity and anxiety-like behavior. To evaluate episodic-like memory, all animals underwent tests to recognize object identity and special location. Lastly, lipid profile and murinometric parameters were evaluated. RESULTS: A two-way ANOVA test followed by a Tukey test demonstrated that the CO&Ex group explored more of the unprotected central area of the OFT (27.04 ± 4.03 s, p < 0.01), when compared to the control group (15.36 ± 2.54 s). CO&Ex spent more time exploring the novel location of the object (71.62 ± 3.04%, p < 0.01), when compared to the control group (58.62 ± 2.48%). DISCUSSION: CO and exercise during lactation can ameliorate the effects of stress on anxiety-like behavior and episodic-like memory in young rats.

Can fish oil supplementation and physical training improve oxidative metabolism in aged rat hearts?

AIMS: It is well known that in the aging process a variety of physiological functions such as cardiac physiology and energy metabolism decline. Imbalance in production and elimination of reactive oxygen species (ROS) may induce oxidative stress. Research shows that oxidative stress is an important factor in the aging process. Studies suggest that É·-3 polyunsaturated fatty acids (PUFAs) and moderate physical exercise modulate the ROS system. Therefore, the present study aimed to investigate whether É·-3 present in fish oil supplementation coupled with moderate physical training could improve antioxidant and metabolic enzymes in the hearts of adult and aged rats and, if these effects could be associated to glycemia, plasma lipid profile or murinometric parameters. MAIN METHODS: Adult (weighing 315.1±9.3g) and aged rats (weighing 444.5±11.8g) exercised and receive fish oil supplementation for 4weeks. Then they were used to evaluate murinometric parameters, fasting glucose and lipid profile. After this, their hearts were collected to measure the levels of malondialdehyde (MDA), antioxidant enzyme activity (superoxide dismutase-SOD, catalase-CAT, glutathione peroxidase-GPx) and oxidative metabolism marker (citrate synthase-CS activity). KEY FINDINGS: Fish oil supplementation increases HDL concentration and activity of CAT and CS. Moreover, physical training coupled with fish oil supplementation induces additional effects on SOD, GPx and CS activity mainly in aged rats. SIGNIFICANCE: Our data suggest that combined treatment in aged rat hearts improves the antioxidant capacities and metabolic enzyme that can prevent the deleterious effects of aging.

Hypercaloric high-lipid diet and brain development: effects on cortical spreading depression in adult rats.

UNLABELLED: Nutritional conditions early in life constitute one of the environmental factors that can influence brain electrophysiology, as evaluated through the phenomenon denominated as cortical spreading depression (CSD). OBJECTIVE: To evaluate the effects of hypercaloric diet intake in different phases of life on CSD features in adult rats. METHODS: Newborn Wistar rats were suckled by dams fed a high-lipid (cafeteria) hypercaloric diet during the lactation period. After suckling, part of the pups remained in the high-lipid diet until the end of the experiment in adulthood (group 'full-life' FL), and the other part received the control (lab chow) diet (group L). A third group received the hypercaloric diet only at adulthood (group Ad). When the animals reached 90-93 days of life, CSD was recorded. RESULTS: CSD propagation velocities (in mm/minute) and CSD amplitudes (in mV) were reduced (P < 0.05) in the groups L (2.77 ± 0.07 and 7.1 ± 2.0 for velocity and amplitude, respectively) and FL (3.05 ± 0.17 and 8.5 ± 1.9), but not in the group Ad (3.36 ± 0.11 and 10.7 ± 2.0), in comparison with a control group (C), fed the lab chow diet during the entire life (3.52 ± 0.18 and 10.8 ± 2.2). DISCUSSION: CSD velocity changes observed in adulthood were associated with the hypercaloric dietary treatment during brain development, constituting evidence in favor of permanent or at least long-lasting electrophysiological effects related to the prevailing nutritional status during the period of brain growth spurt.

Differential effects of physical exercise and L-arginine on cortical spreading depression in developing rats.

OBJECTIVE: We investigated the effect of early-in-life administration of L-arginine, combined with physical exercise, on cortical spreading depression (CSD) in young and adult rats. METHODS: L-arginine (300 mg/kg/day, n = 40) or distilled water (vehicle, n = 40) was given to the rats during postnatal days 7-35 by gavage. Physical exercise (treadmill) was carried out during postnatal days 15-35 in half of the animals in each gavage condition described above. The other half (non-exercised) was used for comparison. When the animals reached 35-45 days (young groups) or 90-120 days of age (adult) CSD was recorded on two cortical points during 4 hours and CSD propagation velocity was calculated. RESULTS: L-arginine-treated + exercised rats had increased body weight, but not brain weight, in adult age compared to L-arginine + non-exercised ones (P < 0.05). In both young and adult animals, L-arginine increased, whereas exercise decreased the CSD propagation velocity. Analysis of variance revealed a significant interaction between gavage treatment and age (P < 0.001), and also between gavage treatment and exercise (P = 0.004), but not between age and exercise. An additional control group of young rats, treated with 300 mg/kg of L-histidine, presented CSD velocities comparable to the corresponding water-treated controls, suggesting that the CSD acceleration seen in the L-arginine group was an L-arginine-specific effect, rather than an effect due to a non-specific amino acid imbalance. DISCUSSION: L-arginine and exercise affect CSD differentially (L-arginine accelerated, while exercise decelerated CSD), and both effects did interact. Probably, they depend on developmental plasticity changes associated with the treatments.

Essential fatty acid deficiency reduces cortical spreading depression propagation in rats: a two-generation study.

Cortical spreading depression (CSD) propagation was investigated in rats under dietary essential fatty acid (EFA) deficiency over two generations (F1 and F2). Wistar rat dams received diets containing 5% fat either from coconut-oil (EFA-deficient) or soybean-oil (control). F1-pups received their dams' diets until the day of CSD recording (30-40 days or 90-100 days). F2-pups were kept on their F1 dams' diet until 30-40 days. Compared to the controls, the EFA-deficient group had reduced (P < 0.05) body weights in both F1 and F2 conditions. This effect was more conspicuous (P < 0.001) in the F2-animals where brain weight was also reduced (P < 0.05). All EFA-deficient groups displayed lower CSD velocities (P < 0.001) than the corresponding controls. Within the same dietary group and generation, F1 young rats showed higher CSD velocities (P < 0.001) than adults. Data show that EFA deficiency reduces CSD propagation, and this effect is long lasting as it persists up to the second generation.

Despite strong behavioral disruption, Delta9-tetrahydrocannabinol does not affect cell proliferation in the adult mouse dentate gyrus.

Marijuana is a widely abused illicit drug known to cause significant cognitive impairments. Marijuana has been hypothesized to target neurons in the hippocampus because of the abundance of cannabinoid receptors present in this structure. While there is no clear evidence of neuropathology in vivo, suppression of brain mitogenesis, and ultimately neurogenesis, may provide a sensitive index of marijuana's more subtle effects on neural mechanisms subserving cognitive functions. We examined the effects of different doses and treatment regimens of Delta(9)-tetrahydrocannabinol (THC), the main active ingredient in marijuana, on cell proliferation in the dentate gyrus of adult male mice. Following drug treatment, the thymidine analog 5-bromo-2'-deoxyuridine (BrdU; 200 mg/kg, i.p.) was administered two hours prior to sacrifice to assess cell proliferation, the first step in neurogenesis. Administration of THC produced dose-dependent catalepsy and suppression of motor activity. The number of BrdU-labeled cells was not significantly changed from vehicle control levels following either acute (1, 3, 10, 30 mg/kg, i.p.), sequential (two injections of 10 or 30 mg/kg, i.p., separated by 5 h), or chronic escalating (20 to 80 mg/kg, p.o.; for 3 weeks) drug administration. Furthermore, acute administration of the potent synthetic cannabinoid receptor agonist R-(+)-WIN 55,212-2 (WIN; 5 mg/kg, i.p.) also had no significant effect on cell proliferation. These findings provide no evidence for an effect of THC on hippocampal cell proliferation, even at doses producing gross behavioral intoxication. Whether marijuana or THC affects neurogenesis remains to be explored.

Fluoxetine inhibits cortical spreading depression in weaned and adult rats suckled under favorable and unfavorable lactation conditions.

Wistar rats (n = 58) were injected subcutaneously during the lactation period with fluoxetine (5, 10, 20 or 40 mg/kg/day) and cortical spreading depression (SD) was recorded immediately after weaning (25-30 days of life). An additional group (10 mg/kg; n = 8) was SD-recorded at 60-70 days. As compared to the saline-injected (n = 24) or "ingenuous" (n = 16) controls, fluoxetine dose-dependently reduced (P < 0.05) SD-velocities in the young rats by 4, 6, 16 and 15%, respectively, and in adult rats by 13%. In another experiment (26 adult rats), topical cortical application of fluoxetine (5 and 10 mg/ml solutions over the intact dura-mater for 10 min; n = 12 and 14, respectively) dose-dependently reduced SD-velocity (7.6% and 43.3% maximal reductions; P < 0.05). SD-propagation was blocked in 4 out of the 14 W-rats topically treated with the highest fluoxetine concentration (10 mg/ml). This topical fluoxetine effect was reverted after flushing the treated region with saline. In additional, 58 early-malnourished rats, fluoxetine applied during the suckling period (10 mg/kg/day, s.c.) and topically (10 mg/ml) also reduced (P < 0.05) SD-velocities by 18 and 22% for the systemic treatment (young and adult animals, respectively) and by 22.4% for the topical one. The present fluoxetine action supports the hypothesis of an antagonistic serotoninergic influence on SD, as previously suggested in experiments using other serotoninergic drugs. Data also suggest that early malnutrition does not greatly affect fluoxetine effects on SD.