The effects of age and lipopolysaccharide (LPS)-mediated peripheral inflammation on numbers of central catecholaminergic neurons

Abstract

Parkinson’s disease (PD), an age-related movement disorder, is characterized by severe catecholaminergic neuron loss in the substantia nigra pars compacta-ventral tegmental area (SNPC-VTA) and locus coeruleus (LC). To assess the stability of these central catecholaminergic neurons following an acute episode of severe inflammation, 6 to 22 month-old C57/Bl6 mice received a maximally tolerated dose of LPS followed by euthanasia two hours later to assay peak levels of peripheral and central cytokines; and, 14 weeks later for computerized stereology of tyrosine hydroxylase-immunopositive (TH+) neurons in the SNPC-VTA and LC. Two hours after LPS, cytokine levels varied in an age-related manner, with the greatest peripheral and central elevations in old and young mice, respectively. Severe inflammation failed to cause loss of TH+ neurons in SNPC-VTA or LC; however, there was an age-related decline in these TH+ neurons in LPS-treated and control groups. Thus, unknown mechanisms in the B6 mouse brain appear to protect against catecholaminergic neuron loss during an acute episode of severe inflammation, while catecholaminergic neuron loss occurs during normal aging.

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“…The total number of TH-immunopositive neurons in the SNpc were quantified using the computerized stereologer system (Stereology Resource Center, Chester, MD, USA) as described previously (Maswood et al, 2004;Mouton et al, 2012). The identification of the SNpc region to be counted on each section was outlined at 2.5× magnification and THimmunopositive neurons were estimated using the dissector probe at 63× oil immersion with a guard volume of 2 μm to avoid sectioning artifacts.…”

In vivo type II T-helper cells shift in schizophrenia compared to sex- and age-matched healthy controls

“…However, IL-4 could also influence the pathology through its impact on IFN-γ/IL-10 and IL-2/IL-4 balance since serum IFN-γ/IL-10 balance were related to symptom severity in females and IL-2/IL-4 ratios to negative symptoms/psychopathology in males with schizophrenia, but not it per se. Diversities between some other studies 15,18,20,21,24,26,41,68,71,74 and ours may be raised by different gender distributions and/or average ages since (1) gender dimorphism during immune responses was observed 75 and (2) cytokine levels could vary in age-related manner 20,76 . The subjects of those studies were either not exactly sex-and/or age-matched or averagely much older than ours.…”

Dysfunctional Sensory Modalities, Locus Coeruleus, and Basal Forebrain: Early Determinants that Promote Neuropathogenesis of Cognitive and Memory Decline and Alzheimer’s Disease

“…NE-dependent modulation of gene transcription, synaptic strength, and other processes clearly reflects a potentially critical role in neuraxis homeostasis (Berridge and Waterhouse 2003;Luo et al 2015). However, there is a progressive atrophy and decline of LC/NE system in aging (Adolfsson et al 1979;Mann et al 1983;Tomonaga 1983;Grudzien et al 2007;Mouton et al 2012). This may cause altered NE transmission that may have extensive ramifications in terms of promotion of a wide variety of disorders.…”

“…The LC neurons in 22-month-old C57/Bl6 mice showed an age-related decline following lipopolysaccharide (LPS)-mediated peripheral inflammation, compared to the 6-month-old animals (Mouton et al 2012). Further, the total number of activated microglia increases substantially greater in aged rats compared to young rats; hence, aging enhances the basal inflammatory state within the BFB (McQuail et al 2010).…”