The Microbiota, Immunoregulation, and Mental Health: Implications for Public Health.

The hygiene or "Old Friends" hypothesis proposes that the epidemic of inflammatory disease in modern urban societies stems at least in part from reduced exposure to microbes that normally prime mammalian immunoregulatory circuits and suppress inappropriate inflammation. Such diseases include but are not limited to allergies and asthma; we and others have proposed that the markedly reduced exposure to these Old Friends in modern urban societies may also increase vulnerability to neurodevelopmental disorders and stress-related psychiatric disorders, such as anxiety and affective disorders, where data are emerging in support of inflammation as a risk factor. Here, we review recent advances in our understanding of the potential for Old Friends, including environmental microbial inputs, to modify risk for inflammatory disease, with a focus on neurodevelopmental and psychiatric conditions. We highlight potential mechanisms, involving bacterially derived metabolites, bacterial antigens, and helminthic antigens, through which these inputs promote immunoregulation. Though findings are encouraging, significant human subjects' research is required to evaluate the potential impact of Old Friends, including environmental microbial inputs, on biological signatures and clinically meaningful mental health prevention and intervention outcomes.

Influence of procedural variables on rat inhibitory avoidance and escape behaviors generated by the elevated T-maze.

A wealth of evidence indicates that changes in procedural parameters and/or environmental conditions may exert a remarkable influence on the basal expression of defensive behaviors in different animal tests of anxiety. The goal of the current study was to further investigate the influence of procedural factors upon inhibitory avoidance acquisition and escape expression of male Wistar rats exposed to the elevated T-maze. These responses have been related in terms of psychopathology to generalized anxiety and panic disorders, respectively. Our results showed that the expression of these behaviors is not affected by prior handling of the animals or by increasing the illumination level of the experimental room from 60 to 580lx. They also showed that enhancing the number of avoidance trials from 3 to 6 favors the acquisition of this behavior. Under this condition, both diazepam (2mg/kg) and clonazepam (1-4mg/kg) caused anxiolytic effects, but only the latter benzodiazepine impaired escape expression, a panicolytic-like effect. In animals exposed to the elevated T-maze whole apparatus 24h before the test, the anxiolytic effect of these drugs was canceled out, which is consistent with the one-trial tolerance phenomenon widely observed in the elevated plus-maze. This procedure, however, does not interfere with the anti-escape effect caused by clonazepam. These results suggest that a 6-trial avoidance learning protocol may be a useful measure for compensating possible individual differences in the acquisition of this defensive response and to improve drug detection in the test.