Several findings relate the hippocampal formation to the behavioural consequences of stress. It contains a high concentration of corticoid receptors and undergoes plastic modifications, including decreased neurogenesis and cellular remodelling, following stress exposure. Various major neurotransmitter systems in the hippocampus are involved in these effects. Serotonin (5-HT) seems to exert a protective role in the hippocampus and attenuates the behavioural consequences of stress by activating 5-HT1A receptors in this structure. These effects may mediate the therapeutic actions of several antidepressants. The role of noradrenaline is less clear and possibly depends on the specific hippocampal region (dorsal vs. ventral). The deleterious modifications induced in the hippocampus by stress might involve a decrease in neurotrophic factors such as brain derived neurotrophic factor (BDNF) following glutamate N-methyl-d-aspartate (NMDA) receptor activation. In addition to glutamate, nitric oxide (NO) could also be related to these effects. Systemic and intra-hippocampal administration of nitric oxide synthase (NOS) inhibitors attenuates stress-induced behavioural consequences. The challenge for the future will be to integrate results related to these different neurotransmitter systems in a unifying theory about the role of the hippocampus in mood regulation, depressive disorder and antidepressant effects.
Several discoveries about leprosy indicate that Mycobacterium leprae transmission mainly occurs by inhalation, and the nose is major port of entry and exit. The present study evaluated the clinical application of PCR for detection of M. leprae DNA in nasal mucosa biopsies in untreated leprosy patients (52) and their contacts (99) from the State Reference Center in Sanitary Dermatology and Leprosy, Uberlandia, MG, Brazil. PCR detection of a 372-base pair DNA fragment from M. leprae was accomplished in 36 (69.2%) patients, from which 34 (91.9%) of them were multibacillaries. Furthermore, PCR was positive in 3 (16.7%) of 18 slit-skin smear negative, 4 (25.0%) of 16 skin lesion BI negative, 8 (33.3%) of 24 nasal mucosa BI negative patients, and 10 of 99 contacts (10.1%). The presence of bacilli in 10.1% of the contacts may potentially reflect an occult leprosy, and these patients must be accompanied, followed by a chemoprophylaxy treatment. Considering all PCR results against clinical and BI classification of patients and controls, we have found a sensitivity of 69.2%, a specificity of 89.9%, and an accuracy of 82.8%. It has been demonstrated here through PCR of nasal biopsies that the bacillus invades the mucosa, passing through the nasal inferior turbinate to reach peripheral blood. Therefore, the molecular investigation of invasive nasal biopsies by PCR tests has proven to be useful in defining patients of higher risk of transmission and risk-group contacts, which is an important step to reach the World Health Organization objective towards the elimination of leprosy as a public health problem.
Recent evidence has suggested that changes in maternal gut microbiota in early life may generate neurobiological consequences associated with psychiatric-related abnormalities. However, the number of studies on humans investigating this problem is limited, and preclinical findings sometimes conflict. Therefore, we run a meta-analysis to examine whether maternal microbiota disturbance (MMD) during neurodevelopment might affect the offspring during adulthood. We found thirteen studies, from a set of 459 records selected by strategy registered on PROSPERO (#289224), to target preclinical studies that evaluated the behavioral outcomes of the rodents generated by dams submitted to perinatal enteric microbiota perturbation. The analysis revealed a significant effect size (SMD = −0.51, 95% CI = −0.79 to −0.22, p < .001, T2 = 0.54, I2 = 79.85%), indicating that MMD might provoke behavioral impairments in the adult offspring. The MMD also induces a significant effect size for the reduction of the sociability behavior (SMD = −0.63, 95% CI = −1.18 to −0.07, p = 0.011, T2 = 0.30, I2 = 76.11%) and obsessive-compulsive-like behavior (SMD = −0.68, 95% CI = −0.01 to −1.36, p = 0.009, T2 = 0.25, I2 = 62.82%) parameters. The effect size was not significant or inconclusive for memory and anxiety-like behavior, or inconclusive for schizophrenia-like and depressive-like behavior. Therefore, experimental perinatal MMD is vertically transmitted to the offspring, negatively impacting behavioral parameters related to psychiatric disorders.