Effects of Estradiol on brain stimulation reward and energy balance in male rats

Like leptin and insulin, estrogen decreases body weight and food intake in male rats; levels of these three hormones vary as a function of fat stores. Thus, it was of interest to determine whether the effect of estrogen on brain stimulation reward (BSR) mimics that of leptin and insulin. The results did not support this prediction: estradiol increased the reward effectiveness of the stimulation in all subjects. The second experiment investigated this relationship by measuring the effect of estradiol implantation on body weight and food intake in ad libitum fed and food restricted male rats. It was found that estrogen further decreased body weight in subjects that had been food-restricted to a level below that of ad libitum fed subjects treated with estrogen. This decrease in body weight is likely due to an increase in energy expenditure. Once ad libitum access to food was restored, the estrogen-treated rats increased their food intake and body weight. This implies that it would be possible to hold constant the weight of food-restricted, estrogen-treated, male rats by adjusting their daily ration. Thus, it should be feasible to investigate the effect of estrogen on BSR in food-restricted male rats whose body weight is held constant. In this way, a direct action of estrogen on the neural substrate for BSR could be distinguished from an indirect influence due to changes in body weight

Role of context, arousal, and female availability in the conditioning of sexual behavior and ejaculatory preference in the male rat

Although male rats are known to display greater unconditional sexual arousal and mating preference to copulate with a novel female compared to a familiar one, research has shown that males given repeated copulatory trials in bi-level chambers with a random almond-scented female develop a conditioned ejaculatory preference (CEP) for females bearing this odor cue. These findings suggest that male rats can learn to associate cues with sexual reward and display preferences for partners that bear those familiar cues. Examination of the effect of copulation in pacing chambers bisected by a divider that either had one hole or four holes at the bottom that only allowed the female to cross, revealed that in 1-hole pacing chambers, females spend more time away from the male than in 4-hole pacing chambers. Males copulating in 1-hole pacing chambers displayed longer ejaculation latencies than those in the 4-hole condition. Interestingly, when animals were changed environments, the differences in ejaculation latencies were maintained suggesting that the pattern of copulation in these males had become conditioned by their initial environment of copulation. An examination of the preferred environment of copulation showed that males prefer to copulate in 4-hole over 1-hole pacing chambers perhaps because males can achieve their optimal rates of copulation in 4-hole chambers. However, contrary to what would be expected, males trained to copulate in 4-hole pacing chambers, with the same almond-scented female at every trial, failed to develop CEP for their familiar female. Instead, it is the males that were trained to copulate in 1-hole pacing chambers that displayed CEP for their familiar female as opposed to the novel one. These findings suggest that copulation in environments in which the female withdraws away from the male for longer periods of time facilitate the development of CEP for a familiar scented female. An analysis of the components required for males to develop CEP for their familiar female revealed that copulation in 1-hole pacing chambers with the same female bearing an olfactory cue and of the same strain as their own are necessary conditions for males to display CEP for their familiar female. Examination of the brain areas involved in the development of CEP for a familiar female, using immunohistochemistry, demonstrated that males that developed CEP for their familiar female displayed significantly more Fos immunoreactivity in the ventral tegmental area (VTA) and in the arcuate nucleus of the hypothalamus (Arc). Pharmacological analyses of the neurochemical mechanisms important for the development of CEP showed that intact opioidergic, but not dopaminergic system, are necessary for the development of CEP in male rats. Examination of neural structures involved in the development of CEP revealed that the VTA and the Arc play an important role in the development of this preference. The present findings shed light on the effect of context on the development of male copulatory behavior and on the development of CEP for a familiar female and its underlying mechanism

An Autopsy Study of Maternal Mortality in Mozambique: The Contribution of Infectious Diseases

Clara Menendez and colleagues analyze 139 complete autopsies following maternal deaths in Maputo, Mozambique and find a predominance of infectious and preventable causes

An autopsy study of maternal mortality in Mozambique: the contribution of infectious diseases

Background Maternal mortality is a major health problem concentrated in resource-poor regions. Accurate data on its causes using rigorous methods is lacking, but is essential to guide policy-makers and health professionals to reduce this intolerable burden. The aim of this study was to accurately describe the causes of maternal death in order to contribute to its reduction, in one of the regions of the world with the highest maternal mortality ratios. Methods and Findings We conducted a prospective study between October 2002 and December 2004 on the causes of maternal death in a tertiary-level referral hospital in Maputo, Mozambique, using complete autopsies with histological examination. HIV detection was done by virologic and serologic tests, and malaria was diagnosed by histological and parasitological examination. During 26 mo there were 179 maternal deaths, of which 139 (77.6%) had a complete autopsy and formed the basis of this analysis. Of those with test results, 65 women (52.8%) were HIV-positive. Obstetric complications accounted for 38.2% of deaths; haemorrhage was the most frequent cause (16.6%). Nonobstetric conditions accounted for 56.1% of deaths; HIV/AIDS, pyogenic bronchopneumonia, severe malaria, and pyogenic meningitis were the most common causes (12.9%, 12.2%, 10.1% and 7.2% respectively). Mycobacterial infection was found in 12 (8.6%) maternal deaths. Conclusions In this tertiary hospital in Mozambique, infectious diseases accounted for at least half of all maternal deaths, even though effective treatment is available for the four leading causes, HIV/AIDS, pyogenic bronchopneumonia, severe malaria, and pyogenic meningitis. These observations highlight the need to implement effective and available prevention tools, such as intermittent preventive treatment and insecticide-treated bed-nets for malaria, antiretroviral drugs for HIV/AIDS, or vaccines and effective antibiotics for pneumococcal and meningococcal diseases. Deaths due to obstetric causes represent a failure of health-care systems and require urgent improvement

The effects of antimicrobials and lipopolysaccharide on acute immune responsivity in pubertal male and female CD1 mice

Exposure to stress during critical periods of development—such as puberty—is associated with long-term disruptions in brain function and neuro-immune responsivity. However, the mechanisms underlying the effect of stress on the pubertal neuro-immune response has yet to be elucidated. Therefore, the objective of the current study was to investigate the effect antimicrobial and lipopolysaccharide (LPS) treatments on acute immune responsivity in pubertal male and female mice. Moreover, the potential for probiotic supplementation to mitigate these effects was also examined. 240 male and female CD1 mice were treated with one week of antimicrobial treatment (mixed antimicrobials or water) and probiotic treatment (L. rhamnosis R0011 and L. helveticus R0052 or L. helveticus R0052 and B. longum R0175) or placebo at five weeks of age. At six weeks of age (pubertal stress-sensitive period), the mice received a single injection of LPS or saline. Sickness behaviours were assessed, and mice were euthanized eight hours post-injection. Brain, blood, and intestinal samples were collected. The results indicated that the antimicrobial treatment reduced sickness behaviours, and potentiated LPS-induced plasma cytokine concentrations and pro-inflammatory markers in the pre-frontal cortex (PFC) and hippocampus, in a sex-dependent manner. However, probiotics reduced LPS-induced plasma cytokine concentrations along with hippocampal and PFC pro-inflammatory markers in a sex-dependent manner. L. rhamnosis R0011 and L. helveticus R0052 treatment also mitigated antimicrobial-induced plasma cytokine concentrations and sickness behaviours. These findings suggest that the microbiome is an important modulator of the pro-inflammatory immune response during puberty

Linking Puberty and the Gut Microbiome to the Pathogenesis of Neurodegenerative Disorders

Puberty is a critical period of development marked by the maturation of the central nervous system, immune system, and hypothalamic–pituitary–adrenal axis. Due to the maturation of these fundamental systems, this is a period of development that is particularly sensitive to stressors, increasing susceptibility to neurodevelopmental and neurodegenerative disorders later in life. The gut microbiome plays a critical role in the regulation of stress and immune responses, and gut dysbiosis has been implicated in the development of neurodevelopmental and neurodegenerative disorders. The purpose of this review is to summarize the current knowledge about puberty, neurodegeneration, and the gut microbiome. We also examine the consequences of pubertal exposure to stress and gut dysbiosis on the development of neurodevelopmental and neurodegenerative disorders. Understanding how alterations to the gut microbiome, particularly during critical periods of development (i.e., puberty), influence the pathogenesis of these disorders may allow for the development of therapeutic strategies to prevent them

The Effects of Probiotic Treatment During Puberty on LPS-Induced Immune Response in Male and Female Mice

Puberty is a critical developmental period that is particularly vulnerable to stress and inflammation. In mice, exposure to an immune challenge (lipopolysaccharide; LPS) during puberty causes enduring effects on depression- and anxiety-like behaviour into adulthood. While the mechanisms underlying these effects remain unknown, the gut microbiome could play a role in mediating the immune system and can alter brain functioning. Thus, we investigated if colonizing the gut with beneficial microbes via probiotics could mediate the inflammatory response to pubertal LPS treatment, in 80 male and female CD1 mice. Sickness behaviour and pro-inflammatory cytokine mRNA expression via RT-qPCR were examined. LPS treatment increased sickness and inflammation in all mice. However, LPS-treated males showed more sickness behaviour, but less central cytokine mRNA expression compared to females and their control saline-treated counterparts. These effects were eliminated when the mice were treated with probiotics. In females, probiotic treatment reduced sickness behaviour, in a time-specific manner, and reduced cytokine mRNA expression in a region-specific manner following LPS treatment. Our results show that probiotics mitigate the LPS-induced immune response differently between males and females. These findings suggest that probiotics have a protective effect during puberty and may prevent the onset of mental health conditions like depression and anxiety.&nbsp

Neurofisiología de la hipersexualidad secundaria al tratamiento de enfermedad de Parkinson

La hipersexualidad puede ser un síntoma secundario al tratamiento de la enfermedad de Parkinson (EP) y forma parte de algunos desórdenes en el control de impulsos en una proporción que va del 20-50% de los pacientes. En esta revisión analizamos las evidencias neurobiológicas que explican el incremento de la hipersexualidad durante el tratamiento con L-DOPA o agonistas dopaminergicos. Se llevó a cabo una búsqueda de información con los términos “Parkinson”, “Hypersexuality”, “Dopamine”, “Noradrenaline”, “L-DOPA”, “Brain”, “Impulse Control Disorders”, “Neurobiology”, buscadas en las bases de datos de PubMed, sciELO y Science Direct. La EP se caracteriza por la pérdida progresiva de neuronas dopaminérgicas de la parte compacta de la sustancia nigra y que proyectan al estriado, produciendo un desbalance en la capacidad motora. Al igual que hace 50 años el tratamiento actual para la EP redunda en el uso de agentes que eleven la disponibilidad de dopamina y otras aminas como la noradrenalina. El tratamiento con L-DOPA o agonistas específicos incrementa los niveles de actividad de dichas aminas incluso en estructuras cerebrales no claramente afectadas por la EP, como las proyecciones tubero-infundibulares y mesolímbicas. El incremento de actividad dopaminérgica en áreas específicas como el núcleo accumbens y el área preóptica/hipotálamo anterior puede explicar la hipersexualidad observada con el incremento súbito en los niveles de motivación y excitación sexual en pacientes tratados para la E