Parkinson's disease manifests as neurological alterations within dendritic spines in the striatal and neocortical brain regions, where their functionality closely correlates with morphology. However, the impact of current pharmacotherapy on dendritic spine neuroplasticity, crucial for novel drug development in neurological and psychiatric disorders, remains unclear. This study investigated the effects of 6-OHDA intrastriatal bilateral lesions in male adult rats on behavior and dendritic spine neuroplasticity in striatal and cortical neurons. Furthermore, it evaluated the influence of chronic co-administration of pramipexole (PPX), a D3 receptor agonist, and rasagiline (Ras), a selective MAO-B inhibitor, on these alterations. Lesioned animals exhibited impaired balance behavior, with no improvement following PPX-Ras treatment. The 6-OHDA lesion decreased dendritic spine density in caudate putamen (CPU) spiny projection neurons (SPNs), a change unaffected by treatment, though PPX-Ras increased mushroom spines and reduced stubby spines in these neurons. In nucleus accumbens (NAcc) SPNs and prefrontal cortex layer 3 (PFC-3) pyramidal cells, dendritic spine density remained unaltered, but PPX-Ras decreased mushroom spines and increased bifurcated spines in the NAcc, while increasing mushroom spines and decreasing stubby spines in PFC-3 in lesioned rats. These findings emphasize the importance of dendritic spines as promising targets for innovative pharmacotherapies for Parkinson's disease.

Locus coeruleus (LC) neurons send their noradrenergic axons across multiple brain regions, including neocortex, subcortical regions, and spinal cord. Many aspects of cognition are known to be dependent on the noradrenergic system, and it has been suggested that dysfunction in this system may play central roles in cognitive decline associated with both normative aging and neurodegenerative disease. While basic anatomical and biochemical features of the LC have been examined in many species, detailed characterizations of the structure and function of the LC across the lifespan are not currently available. This includes the rhesus macaque, which is an important model of human brain function because of their striking similarities in brain architecture and behavioral capacities. In the present study, we describe a method to combine structural MRI, Nissl, and immunofluorescent histology from individual monkeys to reconstruct, in 3 dimensions, the entire macaque LC nucleus. Using these combined methods, a standardized volume of the LC was determined, and high-resolution confocal images of tyrosine hydroxylase-positive neurons were mapped into this volume. This detailed representation of the LC allows definitions to be proposed for three distinct subnuclei, including a medial region and a lateral region (based on location with respect to the central gray, inside or outside, respectively), and a compact region (defined by densely packed neurons within the medial compartment). This enabled the volume to be estimated and cell density to be calculated independently in each LC subnucleus for the first time. This combination of methods should allow precise characterization of the LC and has the potential to do the same for other nuclei with distinct molecular features.

The inferior colliculus (IC), a midbrain hub for integration of auditory information, receives dense cholinergic input that could modulate nearly all aspects of hearing. A key step in understanding cholinergic modulation is to identify the source(s) and termination patterns of cholinergic input. These issues have not been addressed for the IC in mice, an increasingly important model for study of hearing. We examined cholinergic inputs to the IC in adult male and female mice. We used retrograde tracing and immunochemistry to identify three sources of cholinergic innervation of the mouse IC: the pedunculopontine tegmental nucleus (PPT), the laterodorsal tegmental nucleus (LDT) and the lateral paragigantocellular nucleus (LPGi). We then used Cre-dependent labeling of cholinergic neurons in normal-hearing ChAT-Cre mice to selectively label the cholinergic projections to the IC from each of the cholinergic sources. Labeling of cholinergic projections from the PPT and LDT revealed cholinergic axons and boutons terminating throughout the IC, with the ipsilateral projection being denser. Electron microscopic examination showed that these cholinergic axons can form traditional synaptic junctions with IC neurons. In separate experiments, selective labeling of cholinergic projections from the LPGi revealed bilateral projections to the IC. The LPGi axons exhibited relatively equal densities on ipsilateral and contralateral sides, but on both sides the terminations were largely restricted to the non-lemniscal regions of the IC (i.e., the dorsal cortex, lateral cortex and intercollicular tegmentum). We conclude first that cholinergic axons can form traditional synapses in the IC. In addition, lemniscal and non-lemniscal regions of the IC receive different patterns of cholinergic innervation. The lemniscal IC (IC central nucleus) is innervated by cholinergic neurons in the PPT and the LDT whereas the non-lemniscal "shell" areas of the IC are innervated by the PPT and LDT and by cholinergic neurons in the LPGi. DATA AVAILABILITY: Data will be made available on request.

Neuroinflammation associated with microglial activation plays a role in the development of Parkinson's disease (PD). The upregulation of interferon regulatory factor 8 (IRF8) in microglia following peripheral nerve injury has been observed to induce microglial activation. This suggests the potential therapeutic significance of IRF8 in PD. This research aims to explore the effects of IRF8 on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model and lipopolysaccharide (LPS)-induced neuroinflammation, along with its underlying mechanisms. The study examines the differential expression of IRF8 and its effects on neuropathological changes using a PD mouse model and a PD model established from BV2 cells in vitro. IRF8 was found to be prominently expressed in the substantia nigra pars compacta (SNpc) region of PD mice and LPS-stimulated BV2 cells, while the expression of tyrosine hydroxylase (TH) and dopamine (DA) content in the SNpc region of PD mice was notably reduced. MPTP treatment and LPS stimulation intensified microglial activation, inflammation, and activation of the AMPK/mTOR signaling pathway in vivo and in vitro, respectively. Upon IRF8 silencing in the PD mouse and cell models, the knockdown of IRF8 ameliorated MPTP-induced behavioral deficits, increased the counts of TH and Nissl-positive neurons and DA content, reduced the number of Iba-1-positive microglia, and reduced the content of inflammatory factors, possibly by inhibiting the AMPK/mTOR signaling pathway. Similar outcomes were observed in the PD cell model. In conclusion, the suppression of IRF8 alleviates neuroinflammation through regulating microglial activation in PD models in vivo and in vitro by the AMPK/mTOR signaling pathway.

Cross-sectional study.

Cellular ACE2 (cACE2), a vital component of the renin-angiotensin system (RAS), possesses catalytic activity to maintain AngII and Ang 1-7 balance, which is necessary to prevent harmful effects of AngII/AT2R and promote protective pathways of Ang (1-7)/MasR and Ang (1-7)/AT2R. Hemostasis of the brain-RAS is essential for maintaining normal central nervous system (CNS) function. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral disease that causes multi-organ dysfunction. SARS-CoV-2 mainly uses cACE2 to enter the cells and cause its downregulation. This, in turn, prevents the conversion of Ang II to Ang (1-7) and disrupts the normal balance of brain-RAS. Brain-RAS disturbances give rise to one of the pathological pathways in which SARS-CoV-2 suppresses neuroprotective pathways and induces inflammatory cytokines and reactive oxygen species. Finally, these impairments lead to neuroinflammation, neuronal injury, and neurological complications. In conclusion, the influence of RAS on various processes within the brain has significant implications for the neurological manifestations associated with COVID-19. These effects include sensory disturbances, such as olfactory and gustatory dysfunctions, as well as cerebrovascular and brain stem-related disorders, all of which are intertwined with disruptions in the RAS homeostasis of the brain.

Herbert Major (1850-1921) undertook histopathological studies of human and non-human primate brains at the West Riding Lunatic Asylum in Wakefield, England, during the 1870s. Two of his papers specifically investigated the structure of the island of Reil, or insula, "with the view of ascertaining its exact structure". In addition to describing and illustrating its lamination as six-layered, Major also identified "spindle-shaped" cells in the lower layers of human brains, but not in non-human primates. His written description, including measurements of cell body size, and illustration are suggestive that these were the neurones later described in the frontoinsular and anterior cingulate cortex by Constantin von Economo and Georg N. Koskinas and which were subsequently given the eponym "von Economo neurones". von Economo noted that this special neuronal type had been previously seen by Betz (1881), Hammarberg (1895), and Ramón y Cajal (1899-1904), but he did not mention Major's works. Major also ascribed linguistic functions to the insula. Hence, with respect to both anatomical and physiological features, Major may have pre-empted the findings of later research on this structure.

Recent investigations showed the presence of meningeal lymphatic vessels (mLVs) along the superior sagittal and transverse dural sinuses which drain both fluid and immune cells from the cerebrospinal fluid (CSF) to the deep cervical lymph nodes. This study uses immunohistochemistry (IHC) and the Western Blot technique to show the presence of mLV accompanying the dorsal (superior sagittal, inferior sagittal, transverse, sigmoid, and straight) and basal (cavernous, sphenoparietal, superior, and inferior petrosal) dural sinuses in the human brain. Samples for IHC were obtained from dorsal and basal meningeal dural sinuses of 3 human cadavers and 3 autopsies. Routine histological techniques were carried out for the specimens. Podoplanin (PDPN, lymphatic vessel endothelial cell marker) and CD31 (vascular endothelial cell marker) IHC staining were applied to the 5µm thick paraffin sections. Furthermore, PDPN and CD31 protein expressions were evaluated using Western Blot to the tissue samples from the same regions of 4 autopsies. Two consecutive sections from each sinus were PDPN, and CD31 was stained to differentiate blood vessels (BV) from mLV. The IHC staining showed the presence of mLVs accompanying both dorsal and basal dural sinuses. The mLVs accompanying the dorsal dural sinuses had a larger dimensions range compared to the basal dural sinuses. However, the number of mLVs along the basal dural sinuses was more than the mLVs along the dorsal ones. Further, fluid channels were closely localized to the mLV, with varying diameters and densities. Western Blotting technique showed the presence of PDPN expression in both dorsal and basal dural sinus samples. The knowledge of the presence of mLV along both dorsal and basal dural sinuses in humans can increase the understanding of how mLV contributes to the brain lymphatic circulation and may help understand the neuropathophysiological processes of various neurological diseases.