Biology subjects

Dobolyi, A.

Publications and source records attributed to Dobolyi, A..

4 recordsLinked to original sources

bioRxiv2022

Cell-specific expression of key mitochondrial enzymes precludes OXPHOS in astrocytes of the adult human neocortex and hippocampal formation

The astrocyte-to-neuron lactate shuttle hypothesis entails that glycolytically derived pyruvate in astrocytes is converted to lactate instead of being catabolized in mitochondria. The mechanism of this metabolic rewiring is unclear. Here we show that astrocytes of the adult human neocortex and hippocampal formation do not express mitochondrial proteins critical for performing oxidative phosphorylation (OXPHOS) to a detectable degree, including cytochrome c and complex IV. Without OXPHOS, human brain astrocytes are bound to produce lactate to avoid interruption of glycolysis.

neuroscience↗

bioRxiv2022

Anti-glutamatergic effects of three lignan compounds: arctigenin, matairesinol and trachelogenin - An ex vivo study on rat brain slices

Arctigenin is a bioactive dibenzylbutyrolactone-type lignan exhibiting various pharmacological activities. The neuroprotective effects of arctigenin were demonstrated to be mediated via inhibition of AMPA/KA type glutamate receptors in the somatosensory cortex of the rat brain. The aim of this study was to compare the effects of arctigenin with matairesinol and trachelogenin on synaptic activity in ex vivo rat brain slices. Arctigenin, matairesinol and trachelogenin were isolated from Arctium lappa, Centaurea scabiosa and Cirsium arvense, respectively, and applied on brain slices via perfusion medium at the concentration range of 0.5-40 M. The effects of the lignans were examined in the CA1 hippocampus and the somatosensory cortex by recording electrically evoked field potentials. Arctigenin and trachelogenin caused a significant dose-dependent decrease in the amplitude of hippocampal population spikes (POPS) and the slope of excitatory postsynaptic potentials (EPSPs), whereas matairesinol (1 M and 10 M) decreased EPSP slope but had no effect on POPS amplitude. Trachelogenin effect (0.5 M, 10 M, 20 M) was comparable to arctigenin (1 M, 20 M, 40 M) (p > 0.05). In the neocortex, arctigenin (10 M, 20 M) and trachelogenin (10 M) significantly decreased the amplitude of evoked potential early component, while matairesinol (1 M and 10 M) had no significant effect (p>0.05). The results suggest that trachelogenin and arctigenin act via inhibition of AMPA/KA receptors in the brain and trachelogenin has a higher potency than arctigenin. Thus, trachelogenin and arctigenin could serve as lead compounds in the development of alternative neuroprotective drugs.

pharmacology and toxicology↗

bioRxiv2022

Transcriptome profiling of the dorsomedial prefrontal cortex in suicide victims

The default mode network (DMN) plays an outstanding role in psychiatric disorders. Still, gene expressional changes in its major component, the dorsomedial prefrontal cortex (DMPFC), have not been characterized. We used RNA-sequencing in postmortem DMPFC samples to investigate suicide victims compared to control subjects. Most of the data variance (79%) was associated with expression changes between suicide and control samples. 1400 genes differed using log2FC > {+/-} 1 and adjusted p-value < 0.05 criteria between groups. Genes associated with depressive disorder, schizophrenia and impaired cognition were strongly overexpressed in top differentially expressed genes. Gene set enrichment and protein-protein interaction network analysis revealed that pathways related to cytokine receptor signaling were enriched in downregulated while glutamatergic synaptic signaling in upregulated genes in suicide individuals. A validated differentially expressed gene, which is known to be associated with mGluR5, was the N-terminal EF-hand calcium-binding proteins 2 (NECAB2). In situ hybridization histochemistry and immunohistochemistry proved that NECAB2 is expressed in 2 different types of inhibitory neurons located in layers II-IV and VI, respectively. Our results imply extensive gene expressional alterations in the DMPFC related to suicidal behavior. Some of these genes may contribute to the altered mental state and behavior of suicide victims.

neuroscience↗

bioRxiv2022

A thalamo-preoptic pathway promoting social touch

Social touch is an important form of communication, it is still unknown how it is processed. Here, we discovered a functional role for a neuronal pathway projecting from the posterior intralaminar thalamic nucleus (PIL) to the medial preoptic area (MPOA) in controlling social contact. Neurons in the PIL and the MPOA were activated by physical contact between female rodents and also by chemogenetic stimulation of PIL neurons. Chemogenetic stimulation of PIL neurons tagged by social contact experience increased direct physical interactions between familiar female rats without affecting other forms of social behavior. Furthermore, selective stimulation of the PIL-MPOA pathway, and the local activation of PIL terminals within the MPOA, elevated direct social contact between the animals suggesting the role of pathway-specific activated cell assemblies. Neurons projecting from the PIL to the MPOA contain the neuropeptide parathyroid hormone 2 (PTH2). The expression of the peptide was induced by social housing, the presence of PTH2 receptor was identified in MPOA neurons, and local injection of PTH2 increased the firing rate of identified preoptic area GABAergic neurons via the PTH2 receptor suggesting that PTH2 acts as a neurotransmitter in the PIL-MPOA pathway. We also found a homologous PIL to MPOA neuronal pathway in the human brain. Altogether, we discovered a direct thalamo-preoptic pathway, which bypasses the cerebral cortex and controls social touch. This pathway originates in neurons expressing PTH2, a neuropeptide recently shown in fish to respond to the social environment. These observations provide evidence for common evolutionary-conserved PTH2-containing social-touch specific engram circuits.

neuroscience↗