Microbiota changes associated with ADNP deficiencies: rapid indicators for NAP (CP201) treatment of the ADNP syndrome and beyond
Open Access
- 1 February 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Neural Transmission
- Vol. 127 (2), 251-263
- https://doi.org/10.1007/s00702-020-02155-5
Abstract
Activity-dependent neuroprotective protein (ADNP) and its protein snippet NAP (drug candidate CP201) regulate synapse formation and cognitive as well as behavioral functions, in part, through microtubule interaction. Given potential interactions between the microbiome and brain function, we now investigated the potential effects of the ADNP-deficient genotype, mimicking the ADNP syndrome on microbiota composition in the Adnp(+/-) mouse model. We have discovered a surprising robust sexually dichotomized Adnp genotype effect and correction by NAP (CP201) as follows. Most of the commensal bacterial microbiota tested were affected by the Adnp genotype and corrected by NAP treatment in a male sex-dependent manner. The following list includes all the bacterial groups tested-labeled in bold are male Adnp-genotype increased and corrected (decreased) by NAP. (1) Eubacteriaceae (EubV3), (2) Enterobacteriaceae (Entero), (3) Enterococcus genus (gEncocc), (4) Lactobacillus group (Lacto), (5) Bifidobacterium genus (BIF), (6) Bacteroides/Prevotella species (Bac), (7) Clostridium coccoides group (Coer), (8) Clostridium leptum group (Cluster IV, sgClep), and (9) Mouse intestinal Bacteroides (MIB). No similarities were found between males and females regarding sex- and genotype-dependent microbiota distributions. Furthermore, a female Adnp(+/-) genotype associated decrease (contrasting male increase) was observed in the Lactobacillus group (Lacto). Significant correlations were discovered between specific bacterial group loads and open-field behavior as well as social recognition behaviors. In summary, we discovered ADNP deficiency associated changes in commensal gut microbiota compositions, a sex-dependent biomarker for the ADNP syndrome and beyond. Strikingly, we discovered rapidly detected NAP (CP201) treatment-dependent biomarkers within the gut microbiota.Funding Information
- National Science Foundation (BSF-NSF 2016746)
- BMBF (IP7/ 01KI1725D)
- ERA-Net (ADNPinMED)
This publication has 73 references indexed in Scilit:
- Brief Report: The Use of Self-Report Measures in Young People with Autism Spectrum Disorder to Access Symptoms of Anxiety, Depression and Negative ThoughtsJournal of Autism and Developmental Disorders, 2013
- Multiplex Targeted Sequencing Identifies Recurrently Mutated Genes in Autism Spectrum DisordersScience, 2012
- Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsyNeuropsychiatric Disease and Treatment, 2012
- Brain connectivity and high functioning autism: A promising path of research that needs refined models, methodological convergence, and stronger behavioral linksNeuroscience & Biobehavioral Reviews, 2012
- A pilot trial of the microtubule-interacting peptide (NAP) in mice overexpressing alpha-synuclein shows improvement in motor function and reduction of alpha-synuclein inclusionsMolecular and Cellular Neuroscience, 2011
- Excitatory amino acid involvement in dendritic spine formation, maintenance and remodellingJournal Of Physiology-London, 2010
- Expression of Activity-Dependent Neuroprotective Protein in the Immune System: Possible Functions and Relevance to Multiple SclerosisNeuroimmunomodulation, 2009
- Evaluating Dopamine Reward Pathway in ADHDJAMA, 2009
- Activity-Dependent Neuroprotective Protein Snippet NAP Reduces Tau Hyperphosphorylation and Enhances Learning in a Novel Transgenic Mouse ModelThe Journal of pharmacology and experimental therapeutics, 2007
- Activity-dependent neuroprotective protein (ADNP) differentially interacts with chromatin to regulate genes essential for embryogenesisDevelopmental Biology, 2007