Sex-specific and age-related progression of auditory neurophysiological deficits in the Cln3 mouse model of Batten disease / Yanya DING in Journal of Neurodevelopmental Disorders, 17 (2025)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 17 (2025) Titre : Sex-specific and age-related progression of auditory neurophysiological deficits in the Cln3 mouse model of Batten disease Type de document : texte imprimé Auteurs : Yanya DING, Auteur ; Jingyu FENG, Auteur ; Viollandi PRIFTI, Auteur ; Grace A. RICO, Auteur ; Alexander G. SOLORZANO, Auteur ; Hayley E. CHANG, Auteur ; Edward G. FREEDMAN, Auteur ; John J. FOXE, Auteur ; Kuan Hong WANG, Auteur Langues : Anglais (eng) Mots-clés : Animals  Neuronal Ceroid-Lipofuscinoses/physiopathology/genetics  Disease Models, Animal  Female  Mice  Male  Disease Progression  Mice, Knockout  Membrane Glycoproteins/genetics  Molecular Chaperones/genetics  Evoked Potentials, Auditory, Brain Stem/physiology  Electroencephalography  Age Factors  Sex Characteristics  Sex Factors  Auditory brainstem response (ABR)  Auditory evoked potential (AEP)  Duration mismatch negativity (MMN)  Eeg  Translational biomarker  conducted in accordance with ethical standards for the care and use of animals of  the University Committee on Animal Resource (UCAR) at the University of Rochester  Medical Center (URMC, NY). Consent for publication: All authors are consent for  publication. Competing interests: The authors declare no competing financial  interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: CLN3 disease, also known as juvenile Batten disease, is a recessively inherited neurodevelopmental disorder caused by mutations in the CLN3 gene. It represents the most common form of Neuronal Ceroid Lipofuscinoses (NCLs), a group of lysosomal storage disorders that impair brain function. Clinical features include progressive vision loss, language impairment, and cognitive decline. The early onset of visual deficits complicates the neurological assessment of cognitive dysfunction, while the rarity of CLN3 cases limits the study of sex-specific disease trajectories in humans. Therefore, there is a critical need for objective, translational biomarkers to monitor disease progression and support therapeutic development in preclinical animal models. METHODS: Building on our recent studies in individuals with CLN3 disease, we developed a parallel experimental paradigm using high-density electroencephalography (EEG) in Cln3 knockout (Cln3-/-) mice to longitudinally assess auditory neurophysiological changes. We applied a duration-based mismatch negativity (MMN) paradigm, similar to that used in our human studies, to evaluate automatic detection of auditory pattern changes in male and female mice between 3 and 9 months of age. RESULTS: Wild-type (WT) mice of both sexes showed robust and stable duration MMN responses across this age range. In contrast, Cln3-/- mice showed marked sex- and age-dependent deficits: female mutants displayed persistent MMN deficits, whereas male mutants exhibited early MMN abnormalities that unexpectedly improved with age. Auditory brainstem responses confirmed intact peripheral hearing in Cln3-/- mice, indicating a central origin for the observed abnormalities. Further analyses revealed that MMN impairments were driven by age- and sex-specific alterations in auditory evoked potentials to both standard and deviant stimuli. CONCLUSIONS: These findings demonstrate sex- and age-dependent disruptions in central auditory processing in Cln3-/- mice and support auditory duration MMN as a sensitive, translational biomarker of brain dysfunction in CLN3 disease. This approach offers a functional, cross-species measure for tracking disease progression and evaluating therapeutic interventions in Batten disease. En ligne : https://dx.doi.org/10.1186/s11689-025-09652-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] Sex-specific and age-related progression of auditory neurophysiological deficits in the Cln3 mouse model of Batten disease [texte imprimé] / Yanya DING, Auteur ; Jingyu FENG, Auteur ; Viollandi PRIFTI, Auteur ; Grace A. RICO, Auteur ; Alexander G. SOLORZANO, Auteur ; Hayley E. CHANG, Auteur ; Edward G. FREEDMAN, Auteur ; John J. FOXE, Auteur ; Kuan Hong WANG, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 17 (2025) Mots-clés : Animals  Neuronal Ceroid-Lipofuscinoses/physiopathology/genetics  Disease Models, Animal  Female  Mice  Male  Disease Progression  Mice, Knockout  Membrane Glycoproteins/genetics  Molecular Chaperones/genetics  Evoked Potentials, Auditory, Brain Stem/physiology  Electroencephalography  Age Factors  Sex Characteristics  Sex Factors  Auditory brainstem response (ABR)  Auditory evoked potential (AEP)  Duration mismatch negativity (MMN)  Eeg  Translational biomarker  conducted in accordance with ethical standards for the care and use of animals of  the University Committee on Animal Resource (UCAR) at the University of Rochester  Medical Center (URMC, NY). Consent for publication: All authors are consent for  publication. Competing interests: The authors declare no competing financial  interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: CLN3 disease, also known as juvenile Batten disease, is a recessively inherited neurodevelopmental disorder caused by mutations in the CLN3 gene. It represents the most common form of Neuronal Ceroid Lipofuscinoses (NCLs), a group of lysosomal storage disorders that impair brain function. Clinical features include progressive vision loss, language impairment, and cognitive decline. The early onset of visual deficits complicates the neurological assessment of cognitive dysfunction, while the rarity of CLN3 cases limits the study of sex-specific disease trajectories in humans. Therefore, there is a critical need for objective, translational biomarkers to monitor disease progression and support therapeutic development in preclinical animal models. METHODS: Building on our recent studies in individuals with CLN3 disease, we developed a parallel experimental paradigm using high-density electroencephalography (EEG) in Cln3 knockout (Cln3-/-) mice to longitudinally assess auditory neurophysiological changes. We applied a duration-based mismatch negativity (MMN) paradigm, similar to that used in our human studies, to evaluate automatic detection of auditory pattern changes in male and female mice between 3 and 9 months of age. RESULTS: Wild-type (WT) mice of both sexes showed robust and stable duration MMN responses across this age range. In contrast, Cln3-/- mice showed marked sex- and age-dependent deficits: female mutants displayed persistent MMN deficits, whereas male mutants exhibited early MMN abnormalities that unexpectedly improved with age. Auditory brainstem responses confirmed intact peripheral hearing in Cln3-/- mice, indicating a central origin for the observed abnormalities. Further analyses revealed that MMN impairments were driven by age- and sex-specific alterations in auditory evoked potentials to both standard and deviant stimuli. CONCLUSIONS: These findings demonstrate sex- and age-dependent disruptions in central auditory processing in Cln3-/- mice and support auditory duration MMN as a sensitive, translational biomarker of brain dysfunction in CLN3 disease. This approach offers a functional, cross-species measure for tracking disease progression and evaluating therapeutic interventions in Batten disease. En ligne : https://dx.doi.org/10.1186/s11689-025-09652-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

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