Alzheimer\'s disease (AD) is a condition in the brain that is marked by a gradual and ongoing reduction in memory, thought, and the ability to perform simple tasks. AD has a poor prognosis but no cure yet. Therefore, the need for novel models to study its pathogenesis and therapeutic strategies is evident, as the brain poorly recovers after injury and neurodegenerative diseases and can neither replace dead neurons nor reinnervate target structures. Recently, mesenchymal stem cells (MSCs), particularly those from the human olfactory mucous membrane referred to as the olfactory ecto-MSCs (OE-MSCs), have emerged as a potential avenue to explore in modeling AD and developing therapeutics for the disease due to their lifelong regeneration potency and facile accessibility. This review provides a comprehensive summary of the current literature on isolating OE-MSCs and delves into whether they could be reliable models for studying AD pathogenesis. It also explores whether healthy individual-derived OE-MSCs could be therapeutic agents for the disease. Despite being a promising tool in modeling and developing therapies for AD, some significant issues remain, which are also discussed in the review.

Rationale: Adult neurogenesis in the subventricular zone (SVZ) is essential for maintaining neural homeostasis, and its dysregulation contributes to anosmia and delayed tissue healing in neurological disorders, such as Parkinson\'s disease (PD). Despite intricate regulatory networks identified in SVZ neurogenesis, the molecular mechanisms dynamically maintaining neural stem/progenitor cells (NSPCs) in response to physiological and pathological stimuli remain incompletely elucidated. Methods: We generated an RNA binding motif protein 24 (Rbm24) knockout model to investigate its impact on adult neurogenesis in the SVZ, employing immunofluorescence, immunoblot, electrophysiology, RNA-sequencing, and in vitro experiments. Further investigations utilized a PD mouse model, along with genetic and pharmacological manipulations, to elucidate Rbm24 involvement in PD pathology. Results: Rbm24, a multifaceted post-transcriptional regulator of cellular homeostasis, exhibited broad expression in the SVZ from development to aging. Deletion of Rbm24 significantly impaired NSPC proliferation in the adult SVZ, ultimately resulting in collapsed neurogenesis in the olfactory bulb. Notably, Rbm24 played a specific role in maintaining Notch1 mRNA stability in adult NSPCs. The Rbm24/Notch1 signaling axis was significantly downregulated in the SVZ of PD mice. Remarkably, overexpression of Rbm24 rescued disruption of adult neurogenesis and olfactory dysfunction in PD mice, and these effects were hindered by DAPT, a potent inhibitor of Notch1. Conclusions: Our findings highlight the critical role of the Rbm24/Notch1 signaling axis in regulating adult SVZ neurogenesis under physiological and pathological circumstances. This provides valuable insights into the dynamic regulation of NSPC homeostasis and offers a potential targeted intervention for PD and related neurological disorders.

In a real-world environment, the brain must integrate information from multiple sensory modalities, including the auditory and olfactory systems. However, little is known about the neuronal circuits governing how odors influence and modulate sound processing. Here, we investigated the mechanisms underlying auditory-olfactory integration using anatomical, electrophysiological, and optogenetic approaches, focusing on the auditory cortex as a key locus for cross-modal integration. First, retrograde and anterograde viral tracing strategies revealed a direct projection from the piriform cortex to the auditory cortex. Next, using in vivo electrophysiological recordings of neuronal activity in the auditory cortex of awake mice, we found that odor stimuli modulate auditory cortical responses to sound. Finally, we used in vivo optogenetic manipulations during electrophysiology to demonstrate that olfactory modulation in auditory cortex, specifically, odor-driven enhancement of sound responses, depends on direct input from the piriform cortex. Together, our results identify a novel cortical circuit shaping olfactory modulation in the auditory cortex, shedding new light on the neuronal mechanisms underlying auditory-olfactory integration.

The olfactory system plays crucial roles in perceiving and interacting with their surroundings. Previous studies have deciphered basic odor perceptions, but how information processing in the olfactory system is associated with learning and memory is poorly understood. In this review, we summarize recent studies on the anatomy and functional dynamics of the mouse olfactory learning pathway, focusing on how neuronal circuits in the olfactory bulb (OB) and olfactory cortical areas integrate odor information in learning. We also highlight in vivo evidence for the role of the lateral entorhinal cortex (LEC) in olfactory learning. Altogether, these studies demonstrate that brain regions throughout the olfactory system are critically involved in forming and representing learned knowledge. The role of olfactory areas in learning and memory, and their susceptibility to dysfunction in neurodegenerative diseases, necessitate further research.

UNASSIGNED: Fatigue poses risks to occupational health and safety, affecting individuals\' work efficiency, physical health, and social security, as well as human wellbeing and quality of life. Olfactory interventions, due to their low interference, are considered promising strategies for mitigating fatigue and reducing occupational health hazards.
UNASSIGNED: The objective of this review is to bridge the current gaps in the literature by conducting a scoping review of olfactory interventions on human alertness. It aims to explore their application in various occupational settings and to provide comprehensive and practical guidance for the practical application of olfactory interventions in mitigating fatigue and reducing occupational risks.
UNASSIGNED: The literature research was conducted in English using electronic databases such as Web of Science. Keywords related to scent and fatigue and the review followed PRISMA Extension for Scoping Reviews and PICO framework.
UNASSIGNED: 28 studies were included in this work. Participant characteristics, fatigue measurement methods, and scent intervention methods, such as types of scents, intervention strategies, and scent presentation systems, are thoroughly investigated and discussed. Additionally, the study places a specific emphasis on the applications and research within the field of scent interventions for fatigue driving. Olfactory interventions have been applied to populations in various occupational fields, demonstrating beneficial effects on both physiological and psychological fatigue.
UNASSIGNED: Olfactory intervention is effective and promising for enhancing alertness and improving the occupational environment. To provide detailed and practical guidance for the actual application of olfactory intervention in fatigue relief and reducing occupational health and safety hazards, further research into the potential mechanisms, applications, and efficacy assessment systems of fatigue-related olfactory interventions is necessary.

Olfactory sensory neurons (OSNs) are one of a few neuron types that are generated continuously throughout life in mammals. The persistence of olfactory sensory neurogenesis beyond early development has long been thought to function simply to replace neurons that are lost or damaged through exposure to environmental insults. The possibility that olfactory sensory neurogenesis may also serve an adaptive function has received relatively little consideration, largely due to the assumption that the generation of new OSNs is stochastic with respect to OSN subtype, as defined by the single odorant receptor gene that each neural precursor stochastically chooses for expression out of hundreds of possibilities. Accordingly, the relative birthrates of different OSN subtypes are predicted to be constant and impervious to olfactory experience. This assumption has been called into question, however, by evidence that the birthrates of specific OSN subtypes can be selectively altered by manipulating olfactory experience through olfactory deprivation, enrichment, and conditioning paradigms. Moreover, studies of recovery of the OSN population following injury provide further evidence that olfactory sensory neurogenesis may not be strictly stochastic with respect to subtype. Here we review this evidence and consider mechanistic and functional implications of the prospect that specific olfactory experiences can regulate olfactory sensory neurogenesis rates in a subtype-selective manner.

Emotions experienced within sleep mentation (dreaming) affect mental functioning in waking life. There have been attempts at enhancing dream emotions using olfactory stimulation. Odors readily acquire affective value, but to profoundly influence emotional processing, they should bear personal significance for the perceiver rather than be generally pleasant. The main objective of the present sleep laboratory study was to examine whether prolonged nocturnal exposure to self-selected, preferred ambient room odor while asleep influences emotional aspects of sleep mentation and valence of post-sleep core affect. We asked twenty healthy participants (12 males, mean age 25 ± 4 years) to pick a commercially available scented room diffuser cartridge that most readily evoked positively valenced mental associations. In weekly intervals, the participants attended three sessions. After the adaptation visit, they were administered the odor exposure and odorless control condition in a balanced order. Participants were awakened five minutes into the first rapid eye movement (REM) stage that took place after 2:30 a.m. and, if they had been dreaming, they were asked to rate their mental sleep experience for pleasantness, emotional charge, and magnitude of positive and negative emotions and also to evaluate their post-sleep core affect valence. With rs < 0.20, no practically or statistically significant differences existed between exposure and control in any outcome measures. We conclude that in young, healthy participants, the practical value of olfactory stimulation with self-selected preferred scents for enhancement of dream emotions and post-sleep core affect valence is very limited.

UNASSIGNED: Cumulative evidence suggests that sensory cortices interact with the basolateral amygdala (BLA) defense circuitry to mediate threat conditioning, memory retrieval, and extinction learning. The olfactory piriform cortex (PC) has been posited as a critical site for olfactory associative memory. Recently, we have shown that N-methyl-D-aspartate receptor (NMDAR)-dependent plasticity in the PC critically underpins olfactory threat extinction. Aging-associated impairment of olfactory threat extinction is related to the hypofunction of NMDARs in the PC.
UNASSIGNED: In this study, we investigated activation of neuronal cFos and epigenetic marks in the BLA and PC using immunohistochemistry, following olfactory threat conditioning and extinction learning in rats.
UNASSIGNED: We found highly correlated cFos activation between the posterior PC (pPC) and BLA. cFos was correlated with the degree of behavioral freezing in the pPC in both adult and aged rats, and in the BLA only in adult rats. Markers of DNA methylation 5 mC and histone acetylation H3K9/K14ac, H3K27ac, and H4ac exhibited distinct training-, region-, and age-dependent patterns of activation. Strong correlations of epigenetic marks between the BLA and pPC in adult rats were found to be a general feature. Conversely, aged rats only exhibited correlations of H3 acetylations between the two structures. Histone acetylation varied as a function of aging, revealed by a reduction of H3K9/K14ac and an increase of H4ac in aged brains at basal condition and following threat conditioning.
UNASSIGNED: These findings underscore the coordinated role of PC and BLA in olfactory associative memory storage and extinction, with implications for understanding aging related cognitive decline.

UNASSIGNED: Neurogenic orthostatic hypotension (nOH) results from deficient reflexive delivery of norepinephrine to cardiovascular receptors in response to decreased cardiac venous return. Lewy body (LB) forms of nOH entail low 18F-dopamine-derived radioactivity (a measure of cardiac noradrenergic deficiency), olfactory dysfunction by the University of Pennsylvania Smell Identification Test (UPSIT), and increased deposition of alpha-synuclein (ɑ-syn) in dermal sympathetic noradrenergic nerves by the ɑ-syn-tyrosine hydroxylase (TH) colocalization index. This observational, cross-sectional study explored whether combinations of these biomarkers specifically identify LB forms of nOH.
UNASSIGNED: Clinical laboratory data were reviewed from patients referred for evaluation at the National Institutes of Health for chronic autonomic failure between 2011 and 2023. The cutoff value for low myocardial 18F-dopamine-derived radioactivity was 6,000 nCi-kg/cc-mCi, for olfactory dysfunction an UPSIT score ≤ 28, and for an increased ɑ-syn-TH colocalization index ≥ 1.57.
UNASSIGNED: A total of 44 patients (31 LB, 13 non-LB nOH) had data for all 3 biomarkers. Compared to the non-LB group, the LB nOH group had low myocardial 18F-dopamine-derived radioactivity, low UPSIT scores, and high ɑ-syn-TH colocalization indexes (p<0.0001 each). Combining the 3 biomarkers completely separated the groups. Cluster analysis identified 2 distinct groups (p<0.0001) independently of the clinical diagnosis, 1 cluster corresponding exactly to LB nOH.
UNASSIGNED: LB forms of nOH feature cardiac noradrenergic deficiency, olfactory dysfunction, and increased ɑ-syn-TH colocalization in skin biopsies. Combining the data for these variables efficiently separates LB from non-LB nOH. Independently of the clinical diagnosis, this biomarker triad identifies a pathophysiologically distinct cluster of nOH patients.

Hippocampal networks required for associative memory formation are involved in cue- and context-dependent threat conditioning. The hippocampus is functionally heterogeneous at its dorsal and ventral poles, and recent investigations have focused on the specific roles required from each sub-region for associative conditioning. Cumulative evidence suggests that contextual and emotional information is processed by the dorsal and ventral hippocampus, respectively. However, it is not well understood how these two divisions engage in threat conditioning with cues of different sensory modalities. Here, we compare the involvement of the dorsal and ventral hippocampus in two types of threat conditioning: olfactory and auditory. Our results suggest that the dorsal hippocampus encodes contextual information and is activated upon recall of an olfactory threat memory only if contextual cues are relevant to the threat. Overnight habituation to the context eliminates dorsal hippocampal activation, implying that this area does not directly support cue-dependent threat conditioning. The ventral hippocampus is activated upon recall of olfactory, but not auditory, threat memory regardless of habituation duration. Concurrent activation of the piriform cortex is consistent with its direct connection with the ventral hippocampus. Together, our study suggests a unique role of the ventral hippocampus in olfactory threat conditioning.