Loss of prostatic acid phosphatase and α-synuclein cause motor circuit degeneration without altering cerebellar patterning.

Maryam Rahimi-Balaei,Hassan Marzban,Fiona E Parkinson,Pirkko Vihko,Matthew Buchok,Lisa Chakrabarti

doi:10.1371/journal.pone.0222234

Abstract

Prostatic acid phosphatase (PAP), which is secreted by prostate, increases in some diseases such as prostate cancer. PAP is also present in the central nervous system. In this study we reveal that α-synuclein (Snca) gene is co-deleted/mutated in PAP null mouse. It is indicated that mice deficient in transmembrane PAP display neurological alterations. By using immunohistochemistry, cerebellar cortical neurons and zone and stripes pattern were studied in Pap-/- ;Snca-/- mouse cerebellum. We show that the Pap-/- ;Snca-/- cerebellar cortex development appears to be normal. Compartmentation genes expression such as zebrin II, HSP25, and P75NTR show the zone and stripe phenotype characteristic of the normal cerebellum. These data indicate that although aggregation of PAP and SNCA causes severe neurodegenerative diseases, PAP -/- with absence of the Snca does not appear to interrupt the cerebellar architecture development and zone and stripe pattern formation. These findings question the physiological and pathological role of SNCA and PAP during cerebellar development or suggest existence of the possible compensatory mechanisms in the absence of these genes.

Highlights

Alpha- synuclein (SCNA, 140 amino acids) is encoded by Snca gene and is present in the cytoplasm in both free and lipid associated forms [1,2]
In this study to question any neurological abnormalities related to cerebellum, we investigated the cerebellar cortex patterning to indicate any changes in form of stripes and patterns compartmentation in Prostatic acid phosphatase (PAP) mutant mice, to uncover the possible role of PAP and SNCA in the cytoarchitecture and function of the cerebellum
In the cerebellum of control Pap+/+, SNCA was expressed in the axon terminals of the mossy fibers in the granular layer (Fig 1B)

Summary

Introduction

Alpha- synuclein (SCNA, 140 amino acids) is encoded by Snca gene and is present in the cytoplasm in both free and lipid associated forms [1,2]. This protein is one of several major members of intracellular fibrillary proteins, abundant protein in presynaptic axon terminals and important for brain normal function [3]. Synuclein family are comprised of α-, β-, and ɣ-synuclein, and synoretin [4] It was found first in Torpedo californica’s acetylcholine vesicles and suggested to have a role in dopaminergic neurotransmission and synaptic plasticity [3,5].

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