Hi Thomas,

Your question is interesting.

Lately the authors of two articles [REDD1 is essential for stress-induced synaptic loss and depressive behaviour Nature Medicine, 2014, doi:10.1038/nm.3513]and (Multiparametric optical analysis of mitochondrial redox signals during neuronal physiology and pathology in vivo, Nature Medicine, 2014, doi: 10.1038/nm.3520) elucidated your question. Kristie at al al reported that prolonged, ‘hypoxic’ stress is associated with neuronal atrophy of cortical and limbic structures due to increase of an inhibitor of mammalian target of rapamycin complex-1 (mTORC1) in rat PFC. A decrease in phosphorylation of signalling targets of mTORC1 is implicated in protein synthesis-dependent synaptic plasticity deficits. Breckwold at al outlined that mitochondrial redox signal participate in neuronal physiology and disease. During ‘hypoxic’ stress they undergo ‘spontaneous ‘contractions. The contractions are amplified by acute or chronic neuronal insults.

In my article (AS Nikiforova, Stress-induced gastrointestinal motility is responsible for epileptic susceptibility, Medical Hypotheses 82(2014);442-451) I postulate that stress has two phases (mental and emotional). The first phase is ‘non-recognizable’ by CNS i.e. the circular muscles react by prolonged, involuntary high in force ischemic contractions and suppression of their phasic contractions during an uncontrollable stress. A positive feedback loop from gut caused by activation of morphine-receptors’ (MOR) endogenous mediator-modulators sustain the vicious cycle by involving peripheral and interconnected peripheral/brain circuits. The MOR receptors are situated on the surface of glutamergic neurons but not on GABAergic neurons. They endogenous agonists have powerful effect on connection between nucleus Tractus Solitaries (NTS) and dorsal motor nucleus of vagus (DMNV). The opioid peptides inhibit all of the glumatergic currents between the NTS and the DMNV without of need for increasing the activity of cAMP pathway. The inhibition makes synapses unavailable for modulation and low level of c AMP activity keep the MOR inaccessible intracellular compartments. The MOR agonists are available for activation resulting in decrease in the net charge of GABAergic input to DMNV neurons and by thus increase the afferent/efferent input/output of non-cholinergic/non-adrenergic neurotransmitters. The circular ischemic contractions produce specific electrographic changes in gut motility that are mechanotransduced continuously along the engaged circuits. The continuous circulation ensure memorization of the patterns. Due to the suppression of the phasic circular muscles’ contractions the circuits are deprived from ‘burst’ signalization that appears on the depolarised potential of the slow wave. This deprivation might be responsible for apical dendritic shrinking in PFC. Moreover, COOK SC and Wellman CL (Chronic stress alters dendritic morphology in rat medial prefrontal cortex doi:10.1002/neu.20025) reported about reorganization in pyramidal neurons in layer II-III of medial PFC. The authors found out a significant alteration of apical dendrites in stressed animals (the number and length of apical dendritic branches was reduced by 18 and 32% respectively. On the other hand, basiliar dendrites were not affected. Murmi at al (Changes of spine density and dendritic complexity in the prefrontal cortex in offspring of mothers exposed to stress during pregnancy doi:10.111/j.1460-9568.2006.05024.x) found out that the development of layer II-III of pyramidal neurons in dorsal anterior cingulate (ACd) and orbitofrontal cortex (OFC) is significantly affected in offspring of mother exposed to stress during pregnancy. The results showed lower spine density on the apical dendrite as well as in both cortical areas a significant reduction of dendritic length was found in apical dendrites.

Regards,

Assia

Hi Thomas.

A new publication could be helpful: A variant of KCC2 from patients with febrile seizures impairs neuronal Cl− extrusion and dendritic spine formation.

DOI: 10.1002/embr.201438749 |Published 25.03.2014

Regards

Assia