Distinct gradients of various neurotransmitter markers in caudate nucleus and putamen of the human brain

Abstract

The caudate nucleus (CN) and the putamen (PUT) as parts of the human striatum are distinguished by a marked heterogeneity in functional, anatomical, and neurochemical patterns. Our study aimed to document in detail the regional diversity in the distribution of dopamine (DA), serotonin, γ‐aminobuturic acid, and choline acetyltransferase within the CN and PUT. For this purpose we dissected the CN as well as the PUT of 12 post‐mortem brains of human subjects with no evidence of neurological and psychiatric disorders (38–81 years old) into about 80 tissue parts. We then investigated rostro‐caudal, dorso‐ventral, and medio‐lateral gradients of these neurotransmitter markers. All parameters revealed higher levels, turnover rates, or activities in the PUT than in the CN. Within the PUT, DA levels increased continuously from rostral to caudal. In contrast, the lowest molar ratio of homovanillic acid to DA, a marker of DA turnover, coincided with highest DA levels in the caudal PUT, the part of the striatum with the highest loss of DA in Parkinson’s disease (N. Engl. J. Med., 318, 1988, 876). Highest DA concentrations were found in the most central areas both in the PUT and CN. We observed an age‐dependent loss of DA in the PUT and CN that did not correspond to the loss described for Parkinson’s disease indicating different mechanisms inducing the deficit of DA. Our data demonstrate a marked heterogeneity in the anatomical distribution of neurotransmitter markers in the human dorsal striatum indicating anatomical and functional diversity within this brain structure.

Chronic Administration of Fipronil Heterogeneously Alters the Neurochemistry of Monoaminergic Systems in the Rat Brain

“…It is noteworthy that, upon intra-nigral administration, the animals did not exhibit classical signs of experimental parkinsonism, except for the loss of motor coordination and the higher pain sensitivity [ 15 ]. The pattern of striatal DA depletion we report after FPN, mostly medial, does not correspond to the pattern of destruction in Parkinson’s disease, mostly lateral [ 72 ]. However, DA neurons are altered, with profound changes in the correlative pattern of monoamine markers across the brain, which could make our study interesting for the prodromal, pre-symptomatic phase of Parkinson’s disease or Huntington’s disease.…”

Long-term microstructure and cerebral blood flow changes in patients recovered from COVID-19 without neurological manifestations

“…The bilateral thalamus is a susceptible target of ANE related to late immune demyelination in COVID-19 (5) and also brain regions sensitive to hypoxemia. The caudate and putamen as parts of the human striatum are distinguished by a marked heterogeneity in functional, anatomical, and neurochemical patterns (21). For CBF comparisons, the SG showed more widespread CBF decrease in the subcortical nuclei mainly located in the striatum and amygdala compared to the MG.…”

Old neurochemical markers, new functional directions?

“…Numerous studies have revealed the presence of anatomical and biochemical heterogeneity across these regions that underlie functional endpoints and represent challenges to elucidating the neurochemistry, behavior, and pathologies associated with these regions. In this volume of the Journal of Neurochemistry , Hörtnagl, Pifl, Hörtnagl, Reiner, and Sperk () provide an original study that reports the presence of regional heterogeneity in levels of several neurotransmitters, metabolites, or synthetic enymes within the caudate nucleus and putamen of deceased humans with no neurological or psychiatric antecedent. A major focus of the study was devoted to dopamine (DA) and its metabolites homovanillic acid (HVA) and 3,4‐dihydroxyphenyl acetic acid (DOPAC), but analysis was also performed for serotonin (5‐HT) and its metabolite 5‐hydroxyindoleacetic acid (5‐HIAA), gamma‐aminobutyric acid (GABA), and activity of choline acetyl transferase (ChaT) as a marker for acetylcholine.…”

“…Significantly, this approach confers the potential to quantify multiple neurotransmitters and metabolites across the CNS and subterritories of specific brain regions [see for instance the publication of one of the authors (Pifl, Schingnitz, & Hornykiewicz, )], permitting the assessment of neurotransmitter systems in different conditions (Rezai Amin et al, ) and between individuals in distinct cohorts (Dellu‐Hagedorn, Rivalan, Fitoussi, & Deurwaerdere, ; Schepisi et al, ). Here Hörtnagl et al () show that these values can be determined with anatomical precision and permit elucidation of potential relationships between pairs of brain regions that could uncover unsuspected information on functional organization. These approaches may be leveraged in future studies to elucidate new aspects of neuronal activity and to address inter‐individual differences contributing to the complex partnership between homologous and heterologous regulation of terminal function.…”

“…known to result in distinct functional outcomes, and for imbalances in these pathways to contribute to many complex disorders. Here we highlight the study of Hörtnagl et al (2019) who utilize precision dissection of human caudate nucleus and putamen for detailed measurement of major neurochemical markers to address the question of anatomical heterogeneity of neurotransmitter distribution and turnover in these regions. The findings identify gradients of neurotransmitter markers in rostro-caudal, dorso-lateral, and anterior-posterior directions with a precision that has not been previously determined in humans.…”