Beyond Muscular Effects: Depression of Spinal Recurrent Inhibition After Botulinum Neurotoxin A.

Beyond muscular effects: depression of spinal recurrent inhibition after botulinum neurotoxin A.

Filed under: Depression Treatment

J Physiol. 2012 Oct 8;
Marchand-Pauvert V, Aymard C, Giboin LS, Dominici F, Rossi A, Mazzocchio R

The natural target of the botulinum neurototoxin type A (BoNT-A) is the neuromuscular junction. When injected into a muscle, BoNT/A is internalized by motoneurone terminals where it functions as an endopeptidase, cleaving protein components of the synaptic machinery responsible for vesicle docking and exocytosis. As a result, BoNT/A induces a characteristic flaccid paralysis of the affected muscle. In animal models, BoNT/A applied in the periphery can also influence central activity via retrograde transport and transcytosis. An analogous direct central effect in humans is still debated. The present study was designed to address the question whether BoNT-A modifies the activity of the spinal recurrent inhibitory pathways, when injected at muscular level, in humans. To avoid methodological bias, the recurrent inhibition from an injected muscle (soleus) was investigated on an untreated muscle (quadriceps), and stimulation parameters (producing recurrent inhibition) were monitored on a third non injected muscle but innervated by the same nerve as the soleus (flexor digitorum brevis, FDB). The experiments were performed on 14 post-stroke patients exhibiting spasticity in ankle plantarflexors, candidates for BoNT-A. One month after BoNT-A, the level of recurrent inhibition was found depressed. It is suggested that the depression of recurrent inhibition was induced by BoNT/A, injected peripherally, through axonal transport and blockade of the cholinergic synapse between motoneurone recurrent collaterals and Renshaw cells.
HubMed – depression

Differential effects of early environmental enrichment on emotionality-related behaviours in Huntington’s disease transgenic mice.

Filed under: Depression Treatment

J Physiol. 2012 Oct 8;
Renoir T, Pang TY, Mo C, Chan G, Chevarin C, Lanfumey L, Hannan AJ

Psychiatric disorders such as depression and anxiety are reported in Huntington’s disease (HD) patients. Recent studies suggest beneficial effects of environmental enrichment (EE) on HD progression possibly through the serotonergic system. We investigated the potential effectiveness of EE in correcting the affective-like phenotype of female R6/1 HD mice. In addition to a behavioural battery of tests assessing depression and anxiety related endophenotypes, we also recorded physiological measures including body temperature regulation and defecation rate as indices of stress reactivity. Finally, following identification of changes in serotonin receptor gene expression we measured the function of 5-HT1A auto- and hetero-receptors. We found that 8-week-old female HD mice exhibited higher immobility time in the forced-swimming test and a decreased preference for saccharin solution. EE did not correct those depressive-like behaviours but reduced anxiety-related measures in unconditioned approach/avoidance conflict situations. Defecation rate in a large open field and change in temperature during exposure to the tail suspension test were both enhanced in HD compared to WT animals. Despite the enhanced hypothermic response to the 5-HT1A receptor agonist 8-OH-DPAT exhibited by HD mice, we found a reduction in 5-HT1A receptor mediated stimulation of [35S]GTP-?-S binding in the dorsal raphe nucleus and the hippocampus of HD animals. EE did not change 5-HT1A receptor function. Our data suggest that early EE has beneficial effects on the anxiety-like but not on the depression-like behaviours in HD. This is the first evidence that these affective endophenotypes can be dissociated via this form of environmental stimulation. Since 5-HT1A receptor dysfunction was not affected by EE, this receptor is unlikely to underlie the anxiety-related phenotype of HD. However, the specific regulatory role of the 5-HT1A autoreceptor in mediating the depressive-like behaviour in HD remains to be elucidated. Interestingly, by comparing in vivo and in vitro results, our findings suggest that 8-OH-DPAT-induced hypothermia could be mediated by other targets besides the 5-HT1A autoreceptor, including hippocampal 5-HT7 receptors.
HubMed – depression

Differential Mental Health Effects of Neighborhood Relocation Among Youth in Vulnerable Families: Results From a Randomized Trial.

Filed under: Depression Treatment

Arch Gen Psychiatry. 2012 Oct 8; 1-11
Osypuk TL, Tchetgen EJ, Acevedo-Garcia D, Earls FJ, Lincoln A, Schmidt NM, Glymour MM

CONTEXT Extensive observational evidence indicates that youth in high-poverty neighborhoods exhibit poor mental health, although not all children may be affected similarly. OBJECTIVE To use experimental evidence to assess whether gender and family health problems modify the mental health effects of moving from high- to low-poverty neighborhoods. DESIGN Randomized controlled trial. SETTING Volunteer low-income families in public housing in 5 US cities between 1994-1997. PARTICIPANTS We analyze 4- to 7-year outcomes in youth aged 12 to 19 years (n = 2829, 89% effective response rate) in the Moving to Opportunity Study. INTERVENTION Families were randomized to remain in public housing (control group) or to receive government-funded rental subsidies to move into private apartments (experimental group). Intention-to-treat analyses included intervention interactions by gender and health vulnerability (defined as prerandomization health/developmental limitations or disabilities in family members). MAIN OUTCOME MEASURES Past-year psychological distress (Kessler 6 scale [K6]) and the Behavioral Problems Index (BPI). Supplemental analyses used past-year major depressive disorder (MDD). RESULTS Male gender (P = .02) and family health vulnerability (P = .002) significantly adversely modified the intervention effect on K6 scores; male gender (P = .01), but not health vulnerability (P = .17), significantly adversely modified the intervention effect on the BPI. Girls without baseline health vulnerabilities were the only subgroup to benefit on any outcome (K6: ? = -0.21; 95% CI, -0.34 to -0.07; P = .003; MDD: odds ratio = 0.42; 95% CI, 0.20 to 0.85; P = .02). For boys with health vulnerabilities, intervention was associated with worse K6 (? = 0.26; 95% CI, 0.09 to 0.44; P = .003) and BPI (? = 0.24; 95% CI, 0.09 to 0.40; P = .002) values. Neither girls with health vulnerability nor boys without health vulnerability experienced intervention benefits. Adherence-adjusted instrumental variable analysis found intervention effects twice as large. Patterns were similar for MDD, but estimates were imprecise owing to low prevalence. CONCLUSIONS Although some girls benefited, boys and adolescents from families with baseline health problems did not experience mental health benefits from housing mobility policies and may need additional program supports.
HubMed – depression

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